Commentary:Herpes simplex virus and SLE: though uncommon yet with significant implicationsNaim Mahroum1, Abdulrahman Elsalti1, Yehuda Shoenfeld21International School of Medicine, Istanbul Medipol University, Istanbul, Turkey.2Zabludowicz Center for autoimmune diseases, Sheba Medical Center, Ramat-Gan, Israel.Running title : Commentary: Herpes simplex virus and SLE: though uncommon yet with significant implicationsKeywords – Autoimmunity, infection and autoimmunity, systemic lupus erythematosus, human herpes viruses, herpes simplex virus

Evaluating Serum HE4: Some Serious ConsiderationsAimen Waqar Khana, Hussain Haider Shahba: Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.b: Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.Dear Dr Papageorghiou,We have perused with great interest the scholarly article ”Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study” by Chloe Barr et al. [1]. We applaud the authors’ diligent efforts in investigating a biomarker that could independently predict the response to conservative therapy. However, we wish to draw attention to certain noteworthy aspects upon a comprehensive evaluation.Firstly, it is noteworthy that all the women who participated in the study underwent a preliminary endometrial biopsy before the initiation of progestin. However, there is no mention of whether women with relative contraindications such as cervical stenosis, coagulopathy or obstructive cervical lesions were sampled if they were included in the study. It is essential to consider these factors as they can significantly affect the accuracy and reliability of the biopsy results. Furthermore, it is necessary to note that insufficient tissue sampling is a common complication of endometrial biopsy, with an average of 31% of tissues obtained requiring improvement [2]. Considering that this is typically more prevalent in postmenopausal women, and 61% of the participants were 50 years or older, it is crucial to standardize the volume of tissue obtained to ensure fair and precise results. As outlined in the study, the primary form of progestin therapy was levonorgestrel-releasing intrauterine system (LNG-IUS). Still, for women whose devices had been misplaced more than once, an alternative treatment of oral medroxyprogesterone acetate 500mg was administered twice daily. This raises a concern regarding whether these women were closely monitored for compliance with the prescribed treatment regimen. This is particularly important as non-compliance, particularly with extended oral therapies, is a common issue that, if present, could skew the study’s findings. The prognostic potential of pretreatment serum HE4 in predicting therapeutic response has been extensively researched; however, studies have also reported elevated serum HE4 levels in various other cancers, including ovarian, pancreatic, breast, lung, and stomach [3]. Therefore, it is crucial to exclude such patients thoroughly, as their inclusion could lead to inaccurate results by falsely accounting for the non-responder count.Moreover, serum HE4 levels are also known to be influenced by renal function and status, necessitating adjustment [4]. It is, therefore, essential to consider and standardize these factors when analyzing the serum HE4 levels to obtain reliable and valid results. Lastly, it should be noted that a CLEIA technique was employed for analysis, which has been reported to significantly overestimate serum HE4 as compared to EIA [5]. This may raise concerns regarding the validity of the reported findings, and hence, caution must be exercised when interpreting the results.The study focused on endometrial biopsy in women receiving progestin therapy, but potential complications such as insufficient tissue sampling and the inclusion of women with contraindications were not addressed. The study primarily used LNG-IUS but also administered oral medroxyprogesterone acetate, and compliance monitoring was not discussed. Serum HE4 levels were examined, but patients with other cancers or renal issues were not excluded, and the CLEIA technique used for analysis may have overestimated results. Therefore, caution is necessary when interpreting the findings of this study.

TITLE PAGETitle: Comment on: evaluating age and sex-specific rates of gall bladder disease in children with sickle cell diseaseArticle type: Letter to the editorCorrespondence : 1. Ifra Eeman Ahmed contact : 03335890003 Email : ifraeemanahmed786@gmail.comInstitution : Federal medical & dental college,IslamabadAddress: House#2,Street#15g,Sector A,Bahria Enclave,IslamabadCo-author : 2. Satesh KumarContact: +92-3325252902 Email:Institute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa citi Garden east, KarachiWord count: 391Conflict of interest : NoneDeclaration : NoneAcknowledgment : None

Daratumumab induced Minimal Residual Disease Negative Remission in CD 38 (dim) Positive Pediatric Acute Myeloid LeukemiaPronamee Borah1, Dinah Ng1, Nitin Dayal2, Sangeeta Pathak3, Rahul Naithani11Hematology and Bone Marrow Transplant Division, Max Superspecialty Hospital, Delhi, India2Department of Lab Medicine, Max Superspecialty Hospital, Delhi, India3Department of Transfusion medicine, Max Superspecialty Hospital, Delhi, IndiaConflicts of interest: None to declare.No financial support was obtained in this study.Text word count 815Brief running title: Daratumumab in Pediatric AMLKey Words: Daratumumab, AML, ChildrenTables: 0; Figures: 0

Pelvic dimensions and hypotheses on duration of active second stage of labourTilde Broach OstborgStavanger University HospitalTM EggeboTrondheium University HospitalWe would like to thank Jan Novák and Petr Sedlak for their interest and comments to our manuscript. We found that increasing BMI was associated with shorter estimated median duration of the active second stage of labour.1We could not find any obvious causal mechanism for our findings; but suggested some possible explanations. The shorter active second stage may be related to increased abdominal pressure with increasing BMI, or perhaps increased strength when pushing.2, 3 Increased infiltration of fat in the muscular pelvic floor may decrease its strength and resistance.4 The presence of fat in the birth canal of obese women may delay the urge to bear down, thereby postponing active pushing until the head is lower in the maternal pelvis.Novak et al. measured the bi-ilac and bi-cristal diameters of the greater pelvis and found a broader pelvis in individuals with a history of obesity from adolescence.5 We supposed that there would be an association between the size of the greater pelvis and the size of the birth canal. We agree to the limitations commented by Novák and Sedlak. However, our proposed causal mechanisms are merely hypotheses, and cannot be accepted nor rejected based on current knowledge.1. Ostborg TB, Sande RK, Kessler J, Tappert C, von Brandis P, Eggebo TM. Put your weight behind it-Effect of body mass index on the active second stage of labour: A retrospective cohort study. BJOG. 2022;129:2166-2174.2. Lambert DM, Marceau S, Forse RA. Intra-abdominal pressure in the morbidly obese. Obes Surg. 2005;15:1225-1232.3. Tomlinson DJ, Erskine RM, Morse CI, Winwood K, Onambele-Pearson G. The impact of obesity on skeletal muscle strength and structure through adolescence to old age. Biogerontology. 2016;17:467-483.4. Pomian A, Lisik W, Kosieradzki M, Barcz E. Obesity and Pelvic Floor Disorders: A Review of the Literature. Med Sci Monit. 2016;22:1880-1886.5. Novak JM, Bruzek J, Zamrazilova H, Vankova M, Hill M, Sedlak P. The relationship between adolescent obesity and pelvis dimensions in adulthood: a retrospective longitudinal study. PeerJ. 2020;8:e8951.

Very High Power Short Duration Ablation: It Takes Two to Make a Thing Go Right? Samuel D. Maidman, M.D. & Chirag R. Barbhaiya, M.D.From the Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, NYU Langone Health, New York, New York, USA

A 19 year-old adolescent girl with Dravet syndrome, characterized by complex seizure disorder and global developmental delay, presented with B-cell acute lymphoblastic leukemia. The genetic basis for her Dravet syndrome was a pathogenic variant in SCN1A, a sodium channel subunit. SCN1A is chiefly expressed in neuronal tissue, but bioinformatic analysis demonstrated its presence in B cell lineage. One estimate suggested that 10% of children with pediatric cancer have a germline predisposition involving proto-oncogenes or tumor suppressors. This number might be even higher should non-classical genetic variants, such as that encoding a sodium channel subunit, be considered.

Pd-catalyzed asymmetric allylic C−H functionalization has emerged as a powerful tool to access chiral, densely functionalized molecules from easily ac-cessible alkenes, enabling the increase of the step- or atom-economy by minimizing functional group manipulations for preparing allylating reagents. Due to the inadequacy of stereoselection strategies, the asymmetric allylic C-H functionalization is still in the early stage. In this essay, we will describe our journey to identification of asymmetric catalytic systems, mechanism of allylic C−H activation, control of stereo- and regioselectivity, and applica-tions in asymmetric synthesis.

Dear Editor, We read with great interest the article recently published in Journal of Cardiovascular Electrophysiology, “Left atrial appendage dimension predicts elevated brain natriuretic peptide in nonvalvular atrial fibrillation” by Cook JA. et al. 1 The authors have studied the relation between Brain natriuretic peptide (BNP) elevations and left atrial appendage measurements in patients who referred for left atrial appendage (LAA) occlusion in patients with nonvalvular atrial fibrillation (AF). BNP release is largely from the ventricles and it is also dynamically dependent on myocardial stretch and fluid volume status. However, it seems difficult to prove that BNP levels are directly related to the LAA measurements. Correlating BNP elevation only with left atrial or LAA measurements means ignoring left ventricular strain. Considering that these patients were referred for LAA occlusion and had a high CHA 2DS 2-VASc score, and not taking heart failure with preserved ejection fraction into account may lead to errors in interpreting the results. Moreover, it should be evaluated that the left atrial appendage may undergo remodeling or enlargement as a result of the left ventricular end-diastolic pressure increase. In this case, although the study is valuable, remains a cross-sectional study and a snapshot of the correlation of BNP and LAA. Second, it should be disclosed whether patients have paroxysmal or chronic AF and how long the patient has had AF. A relationship was established between LAA dimensions and BNP in the study, it is essential that the duration of AF should be considered and subgroup analyses should be evaluated if possible, since AF has a significant effect on BNP release. We appreciate this study and believe that a more detailed evaluation including left ventricular evaluation and prospectively monitored LAA and BNP would yield more realistic results. In addition, we think that it would be useful to evaluate midregional pro-A-type natriuretic (MR-proANP) in LAA studies, which is specific to the left atrial enlargement and similar physiology to BNP. 2

The conflict in Ukraine, which started when Russia invaded and violated its sovereignty, has led to the country's worst war since the annexation of Crimea in 2014. The war has resulted in a significant number of casualties, displaced millions of people, and damaged the healthcare system, which was already struggling before the conflict. The neurosurgical field, in particular, has been severely affected, with infrastructure and healthcare systems routinely demolished or interrupted in conflict zones, making fundamental medical operations unavailable to victims of armed conflict. As a result, neurosurgeons have been compelled to conduct surgeries outside of their areas of competence, in makeshift settings or under challenging conditions, with limited access to materials and equipment. The war has also severely damaged specialized neurosurgery facilities, causing a severe shortage of crucial supplies and equipment. To address the challenges facing neurosurgery care in Ukraine, it is essential to rebuild and repair the damaged neurosurgical centers and provide them with the necessary equipment and supplies to successfully administer neurosurgical treatments. Training programs for neurosurgeons and other medical specialists must also be organized to manage complex neurosurgical problems under difficult conditions.

In the production of biopharmaceuticals depth filters followed by sterile filters are often employed to remove residual cell debris present in the feed stream. In the back drop of a global pandemic, supply chains associated with the production of biopharmaceuticals have been constrained. These constraints have limited the available amount of depth filters for the manufacture of biologics. This has placed manufacturing facilities in a difficult position having to choose between running processes with reduced number of depth filters and risking a failed batch or the prospect of plants going into temporary shutdown until the depth filter resources are replenished. This communication describes a modeling based method that leverages manufacturing scale filtration data to predict the depth filter performance with a reduced number of filters and an increased operational flux. This method can be used to quantify the acceptable level of area reduction before which the filtration process performance is affected. This enables facilities to manage their filter inventory avoiding potential plant shutdowns and reduces the risks of negative depth filter performance.

Osteogenesis imperfecta (OI) is a rare disorder of bone fragility. Gravid patients with OI usually need cesarean and may present multiple challenges. We present a case of an OI patient with severe scoliosis and an anticipated difficult airway undergoing cesarean section, with details on perioperative assessment and strategy of anesthesia.

The ancient Greeks took the entertainment of their crowds very seriously and used drama as a way of investigating the world they lived in. The theatrical re-enactment of suffering and grief in front of a large audience was to foster compassion, as well as a cathartic release of emotion that was restorative through a deeply felt interconnection between actors and audience. When our patients encounter tragedy, we are also drawn into their ordeal and experience it first hand. Such it was with Rose.

One hundred fecal samples from hooded vultures in the Gambia (Banjul area) were investigated for the presence of bacteria with extended-spectrum cephalosporin- (ESBL/AmpC), carbapenemases, and colistin resistance. No Enterobacteriales carrying carbapenemases or resistance against colistin were detected. Fifty-four ESBL-producing Escherichia coli and five ESBL-producing Klebsiella pneumoniae isolates were identified in 52 of the samples, of which 52 E. coli and 4 K. pneumoniae yielded passed sequencing results. Fifty of the E. coli had ESBL phenotype and genotype harboring blaCTX-M genes, of which 88.5% (n=46) were the blaCTX-M-15 gene, commonly found on the African continent. Furthermore, the genetic context around blaCTX-M-15 was similar between isolates, being co-localized with ISKpn19. In contrast, cgMLST analysis of the E. coli harboring ESBL genes revealed a genetic distribution over a large fraction of the currently known existing E. coli populations in the Gambia. Hooded vultures in the Gambia thus have a high ESBL E. coli-prevalence (>50%) with low diversity regarding key resistance genes. Furthermore, given the urban presence and frequent interactions between hooded vultures and humans, data from this study implies hooded vultures as potential vectors contributing to the further dissemination of antibiotic-resistance genes.

SARS-CoV-2 causes COVID-19 pandemic and continues to pose a threat to global public health through genetic mutation. In this study, we have found that an ACE2-specific monoclonal antibody at low concentration was able to greatly enhance SARS-CoV-2 infection and growth in cell culture. Strikingly, it promotes SARS-CoV-2 plaque formation, resulting in accurate titration of different SARS-CoV-2 variants, particularly the newly emerged Omicron variants, which otherwise cannot be determined by standard plaque assays. Quantification of infectious titers of the newly emerged variants will facilitate the development and evaluation of vaccines and antiviral drugs against SARS-CoV-2.

A 65 year-old with history of prior ablations for regular narrow QRS short- RP tachycardia presented with recurrence of palpitations. An electrophysiological study showed long VA tachycardia with concentric atrial activation with a left ventricular origin extrastimulus delivered during His refractoriness, advancing the next ‘A’. A HRVPB can only reset an ORT if it ‘pulls in’ the local V at the ventricular insertion of an accessory pathway. As showcased in this case, erudite analysis of the pattern of perturbation of local ventricular electrograms is of paramount significance when interpreting responses to this maneuver. This concept when fortified with a heightened index of clinical suspicion for mitral annular block, anatomical knowledge of the pattern of LA-CS muscular connections, and pathway orientation, led to accurate electrophysiological diagnosis and management.

Letter to the editor

A 5-month-old male baby was brought to the emergency room with a one-day history of respiratory distress, wheezing, vomiting, and high fever. Wheezing had been present since birth but had recently become more frequent and intense, occurring even at rest. The baby was born full-term by cesarean delivery and had a medical history of gallbladder agenesis, secundum atrial septal defect (ASD), and cryptorchidism.