ADVANCEMENTS IN MARBURG VIRUS VACCINE DEVELOPMENT: UNRAVELLING RECENT FINDINGS. A NARRATIVE REVIEW.

Marburg Virus Disease (MVD) is a lethal single-stranded RNA virus transmitted by Egyptian rousette bats, causing 12 surges in Sub-Saharan Africa, including a recent outbreak in Tanzania in 2023. With a fatality rate of approximately 90%, no approved vaccines currently exist. Ongoing research explores potential candidates, such as a recombinant vesicular stomatitis virus (VSV)-based vaccine and MVA-BN-Filo, aiming to combat this deadly infection. The objective of this review is to comprehensively examine Marburg virus vaccines, exploring various candidates and their development stages, efficacy in non-human primates and human studies, and challenges faced in the development process. Various vaccines are under development, including Ad26, Ad5, viral vector, and DNA vaccines. Promising candidates like Ad26.Filo and ChAd3-MARV have emerged. Additionally, VLP-based, DNA plasmid and rVSV-based vaccines are discussed, highlighting their effectiveness and challenges in development, such as limited information, gene expression issues, and outbreak control measures. The implications for future research and clinical practice/policy development are significant. Marburg virus vaccine development shows promise in mitigating the threat posed by this deadly pathogen. Despite complex challenges, advancements in vaccine candidates offer hope. Continued research and development may lead to the successful prevention of major Marburg virus outbreaks. Ongoing clinical trials indicate potential breakthroughs in a short period, contributing to public health protection.    

Preoperative anxiety management in pediatric patients: a systemic review and meta-analysis of randomized controlled trials on the efficacy of distraction techniques

BackgroundThis study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients.MethodsFollowing the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979).ResultsThis meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias.ConclusionOur study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=449979, PROSPERO [CRD42023449979]

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

An indispensable revolution for Pakistan, the beginning of robot assisted MIMVS

Madam, Minimally invasive surgical (MIS) techniques or ‘sternal sparing’ strategies, performed by making minor right chest incisions, were introduced in the mid-1990s [1,3]. From that point forward, there has been a decrease in surgical injury and postoperative recuperation, coming about in expanded acknowledgement of these approaches. It works on three essential standards: rebuilding and conserving MV pamphlet portability, creating a vast flyer coaptation surface, and remodeling of the mitral annulus to supply an ideal and steady orifice area. [1] The history of MIMVS expanded from the 1990s when minimally invasive approaches such as the parasternal incision, hemi sternal incision and the mini thoracotomy were investigated by autonomous groups led by Delos Cosgrove and Lawrence Cohn. Further advancements include the primary video-directed repair and substitutions performed through a mini-thoracotomy and the primary utilization of end balloon clamping. Later, improvements incorporated the coming of stereoscopic 3D video endoscopy and mechanical surgery. [5] Robotic technology facilitates complex surgical procedures on the mitral valve without opening the chest. The most significant advantage is diminished surgical injury, which deciphers into early recuperation. In 1998, robotic mitral valve repair was initiated and adopted in 2005 by the US following the first multicenter trial. In classic robotic mitral valve surgery, femoral-femoral cardiopulmonary machine cannulation is performed through a small incision in the groin. The surgeon leading the robotic mitral valve surgery must have the relevant heart surgery certification from the country's certifying institution. The console surgeon should be experienced in all aspects of mitral valve surgery and be highly versed in repair techniques as robotic procedures take longer than traditional surgeries, especially during the learning curve. Apprenticeship in the so-called mini-mitral using conventional videoscopy is also an advantage, but not a mandatory requirement The courses on robotic mitral valve surgery including formal didactic and practice-oriented training should be obtained by the lead surgeon and the team. Virtual stimulators and wet labs should be provided by the hospital to the team to practice their first 8-10 cases until they gain expertise ---Continu

Functional outcomes in proximal humerus fractures: a prospective registry-based analysis

Objective: To evaluate clinical and functional outcomes of proximal humerus fractures managed with different procedures and determining factors influencing outcomes. Methods: Data of this prospective cohort was obtained from the orthopaedic trauma registry at a tertiary care Hospital from June 2015 to October 2019. Sixty-nine adult patients with proximal humerus fracture managed either surgically or non-operatively were identified. Functional and clinical outcomes had been assessed using Quick Disability of the Arm, Shoulder and Hand score. Outcomes were assessed up to 12 months follow-ups and were compared between different treatment groups and between isolated versus proximal humerus with additional upper limb fractures. Results: In the 69 patients, 31 (45%) belonged to >55 years age group. Fifty-eight (84%) patients were operated of which 43 (62%) underwent Proximal Humeral Internal Locking System procedure. There was non-significant difference in clinical and functional outcomes between isolated versus proximal humerus fractures associated with other upper limb fractures at follow-ups 6 weeks onwards. At 3 months follow-up, there was significantly better outcomes in all treatment groups compared to PHILOS with bone graft/BMP (p=0.004-0.035). Males had significantly better recovery at 3 months as compared to females (p=0.04).  Continuous..

Model for detecting metastatic deposits in lymph nodes of colorectal carcinoma on digital/ non-WSI images

Introduction: Colorectal cancer (CRC) constitutes around 10% of global cancer diagnoses and death due to cancer. Treatment involves the surgical resection of the tumor and regional lymph nodes. Assessment of multiple lymph node demands meticulous examination by skilled pathologists, which can be arduous, prompting consideration for an artificial intelligence (AI)-supported workflow due to the growing number of slides to be examined, demanding heightened precision and the global shortage of pathologists.Method: This was a retrospective cross-sectional study including digital images of glass slides containing sections of positive and negative lymph nodes obtained from radical resection of primary CRC. Lymph nodes from 165 previously diagnosed cases were selected from Agha Khan University Hospital, from Jan 2021 to Jan 2022. The images were prepared at 10X and uploaded into an open source software, Q path and deep learning model Ensemble was applied for the identification of tumor deposits in lymph node.Results: Out of the 87 positive lymph nodes detected by AI, 73(84%) were true positive and 14(16%) were false positive. The total number of negative lymph nodes detected by AI was 78. Out of these, 69(88.5%) were true negative and 9 (11.5%) were false negative. The sensitivity was 89% and specificity 83.1%. The odds ratio was 40 with a confidence interval of 16.26-98.3. P-value was \u3c 0.05 (\u3c 0.0001).Conclusion: Though it was a small study but its results were really appreciating and we encourage more such studies with big sample data in future

Toxic elements identified in breast milk of mothers residing in water contaminated region of Sindh and their impact on infants’ growth patterns: A case-control study

Breast milk is a vital source of nutrition for breastfed infants, providing essential nutrients and elements but, in some cases, toxic ones. This is the first case-control study that investigated the elemental profile of breast milk samples collected from mothers residing in Matiari (Sindh), a region with insufficient industrial waste management, and its potential impact on infants\u27 anthropometrics. Precisely, 62 milk samples, including 42 cases and 20 controls, were analyzed using the ICP-MS technique. Overall, six elements showed significance between the two groups, arsenic (As) was present at 0.68 μg/L in cases and absent in controls, while lead (Pb) exhibited elevated concentrations in the case group at 4.56 μg/L compared to 0.25 μg/L in controls, well-known for their toxicity. Barium (Ba) and manganese (Mn) levels were also higher in cases, associated with reported health effects on child well-being. Essential elements molybdenum (Mo) and selenium (Se) were higher in the controls. Furthermore, the association of these metals with the child growth standards as per WHO guidelines was calculated. Linear regression analysis revealed As negatively associated with WAZ and WHZ scores, while Mo was positively associated with WAZ, WHZ, and HAZ scores. These findings highlight serious health concerns in the region, where toxic elements pervade drinking water and food sources. Immediate actions are imperative to maintain the wellness of future generations

Polymorphism of the renalase gene in gestational diabetes mellitus

Renalase is considered as a novel candidate gene for type 2 diabetes. In this study, we aimed to investigate the relationship of serum renalase and two single nucleotide polymorphisms with gestational diabetes mellitus. One hundred and ninety-eight normotensive pregnant females (n=99 gestational diabetes mellitus; n=99 euglycemic pregnant controls) were classified according to the International Association of the Diabetes and Pregnancy Study criteria. Fasting and 2-h post glucose load blood levels and anthropometric assessment was performed. Serum renalase was measured using enzyme-linked immunosorbent assay, whereas DNA samples were genotyped for renalase single nucleotide polymorphisms rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment length polymorphism method. In an age-matched case control study, no difference was observed in the serum levels of renalase (p\u3e0.05). The variant rs10887800 showed an association with gestational diabetes mellitus and remained significant after multiple adjustments (p\u3c0.05), whereas rs2576178 showed weak association (p=0.030) that was lost after multiple adjustments (p=0.09). We inferred a modest association of the rs10887800 polymorphism with gestational diabetes. Although gestational diabetes mellitus is self-reversible, yet presence of this minor G allele might predispose to metabolic syndrome phenotypes in near the future