Pharmacological venous thromboembolism prophylaxis in elective cranial surgery: a systematic review of time of initiation, regimen and duration.

INTRODUCTION: Pharmacological prophylaxis of venous thromboembolism (VTE) requires nuanced decision-making to balance the risk of VTE against haemorrhage. This problem is compounded in neurosurgical patients, in whom postoperative intracranial haemorrhage (ICH) may be catastrophic, compared to non-neuraxial bleeding in other types of surgery. Current major guidelines recommend caution when using pharmacological prophylaxis in elective cranial surgery, but incorporate low-quality evidence and lack precise guidance on timing and duration of anticoagulation. METHODS: We aimed to answer the following questions for patients undergoing elective cranial surgery: (1) when is the optimal time to initiate postoperative anticoagulation, and (2) how long should postoperative anticoagulation be continued for? In this systematic review, we screened randomised and non-randomised studies reporting original data on pharmacological VTE prophylaxis in elective cranial surgery. Outcomes of interest were VTE and ICH. RESULTS: Three retrospective, single-centre observational studies met eligibility criteria, with a total of 923 participants. Meta-analysis was not performed due to a high risk of bias across all studies. Through narrative synthesis, we found that patients who developed VTE were significantly more likely to receive their first postoperative dose at a later time (mean: 144 vs. 29 h, p = .04). Shorter courses of anticoagulation (<7 days) were associated with significantly lower ICH rates (p = .03) compared to longer courses (>21 days). CONCLUSION: The limited evidence favours earlier initiation and shorter courses of thromboprophylactic anticoagulation. These findings are specific to patients undergoing surgery for meningioma or glioma and may not apply to other populations. Randomised controlled trials or robustly designed observational studies are necessary to establish a clearer evidence base.

Human leukocyte antigen association with familial steroid-sensitive nephrotic syndrome.

Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood. Cases with the familial occurrence of SSNS suggest that genetics may play a role in the disease. Human leucocyte antigen (HLA) alleles have been associated with SSNS. We present genetic findings in nine families (44 participants), each with at least two affected siblings. A total of 19 patients were affected with familial SSNS. Six of nine families showed linkage to markers on chromosome 6p (27.29-33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. Interestingly, we also found linkage of disease phenotype of familial SSNS on chromosome 15 (91.7-96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score Z = 3.02.Conclusion: Our findings confirm the linkage of HLA markers on chromosome 6, which strengthens the association of HLA alleles in SSNS. What is Known: • Human leukocyte antigen (HLA) alleles have been associated with idiopathic steroid-sensitive nephrotic syndrome (SSNS). Only few studies have investigated the association between HLA alleles and familial SSNS. What is New: • We present evidence of linkage of familial SSNS to chromosome 6p (27.29-33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. We also found linkage of the disease phenotype of familial SSNS on chromosome 15 (91.7-96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score of Z = 3.02 following autosomal recessive inheritance pattern.

Childhood onset steroid-sensitive nephrotic syndrome continues into adulthood.

BACKGROUND: Childhood steroid-sensitive nephrotic syndrome (SSNS) has previously been assumed to be a disease of childhood. This has been challenged by few studies reporting that some patients with childhood SSNS may continue to relapse into adulthood. The aim of this study was to investigate the long-term outcome of childhood SSNS presenting data from an unselected well-defined cohort of Danish patients. METHODS: We conducted a retrospective study of the clinical outcome from a population of patients consecutively admitted to the pediatric departments in the central and northern region of Denmark from 1998 to 2015. Patients were followed until August 2017. Data were collected from the patient's medical records. RESULTS: Long-term outcome was studied in 39 adult patients with childhood onset SSNS. A total of 31% (12/39) had active disease in adulthood. Univariate analysis showed that more severe forms of SSNS (e.g., steroid dependent/frequent relapsing (SD/FR) nephrotic syndrome) in childhood were associated with active disease in adulthood. Comparing adult patients with SD/FR showed a significantly higher number of relapses/patient/year from late childhood and adolescence in the group with active disease vs. non-active disease (1.06 (95%CI: 0.32-1.81) vs. 0.19 (95%CI: 0.06-0.31, p = 0.005). CONCLUSION: In general, one third of all patients with SSNS during childhood continue to have active disease during early adulthood, in particular patients with SD/FR continue to suffer from active disease. The present data illustrates that SSNS is not just a disease of childhood but persists in adulthood in a significant number of patients.

Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus.

Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI. CONCLUSION: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • We identified eight novel disease-causing variants in AVPR2: p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.

Cataract surgery outcomes in pediatric patients with systemic comorbidities.

Purpose: The aim of the study was to evaluate the outcomes of cataract surgery in patients of the pediatric age group with systemic comorbidities. Methods: Medical records of 54 eyes (30 patients) of the pediatric age group with systemic comorbidities who had undergone cataract surgery in a tertiary-care center were reviewed. The following parameters were recorded: systemic comorbidity; toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV (TORCH) profile, best spectacle-corrected visual acuity (BSCVA), strabismus, nystagmus, and cataract morphology. Results: Thirty patients with a mean age of 55 months (9 months-14 years) were included. On average, every child was seen by three physicians, and the mean duration between the first visit to a physician and presentation to our center was 2.23 ± 0.67 years. The various causes for delay in referral include multiple referrals due to a lack of general anesthesia services in 78% of cases, a long waiting list at the referral hospital in 35% of cases, and a lack of awareness at the primary-care physician level in 50% of cases. The mean BSCVA at presentation was 1.4 logMAR (0.3 to 3 logMAR). The most common cataract morphology was that of zonular cataract (31.48%; 17/54). Strabismus and abnormal eye movements were observed in 27.7% (15/54) and 33.3% (18/54) of eyes, respectively. Various systemic associations were periventricular leukomalacia (12/30), Down's syndrome (6/30), seizure disorder (6/30), cardiac valvular anomalies (6/30), Marfan's syndrome (4/30), hypothyroidism (4/30), rubella (3/20), cytomegalovirus (3/20), cerebral palsy (2/30), nephrotic syndrome (2/30), Type 1 diabetes mellitus (1/30), microcephaly (1/30), cryptogenic West syndrome (1/30), congenital rubella syndrome (1/30), and Tourette syndrome (1/30). The mean postoperative corrected distance visual acuity (CDVA) at 2-year follow-up improved to 1.0 logMAR (0 to 3 logMAR). No postoperative complications were reported at the final follow-up. Around 70% of the parents reported improvement in their child's psychomotor skills. Conclusion: Intellectually impaired pediatric patients with cataract should be operated upon whenever there is a presence of infrastructure, and unnecessary delay in surgery should be avoided by referring the patient to higher centers. Even though objective improvement in visual acuity was suboptimal, there was definitely an improvement in the psychomotor skills of the patients.

Current Attitudes Toward Neuroanatomy: A Comparative Cross-Sectional Survey of Neurosurgeons from the United Kingdom and Worldwide.

OBJECTIVE: How attitudes toward neuroanatomy and preferences of studying resources vary among neurosurgeons is unknown. The impact of the coronavirus disease 2019 (COVID-19) pandemic on anatomy learning habits is also yet to be elucidated. In this study, we explore these objectives, to guide the development of future neurosurgeon-tailored anatomy education and resources. METHODS: This was a 2-stage, cross-sectional study design comprising a local pilot survey followed by a structured 17-item questionnaire, distributed to both neurosurgical trainees and consultants. Grade and nationality differences in sentiment agreement were statistically compared. RESULTS: A total of 365 responses were received from 32 countries (overall response rate, 23.2%). Neuroanatomy is highly regarded among most neurosurgeons and takes a central role in their professional identity. Yet, 69% of neurosurgeons wanted to spend more time learning. Common study prompts included perceived operative complexity, lack of familiarity and teaching. Financial barriers and motivation were obstacles limiting neuroanatomy learning, more so among trainee neurosurgeons, with personal commitment barriers significantly varying with geographic location. Surgical relevance, accessibility, and image quality were important factors when selecting anatomy resources, with cost and up-to-datedness being important for juniors. The COVID-19 pandemic saw a shift toward virtual resources, particularly affecting United Kingdom-based trainees. CONCLUSIONS: Although neuroanatomy is well regarded, barriers exist that impede further neuroanatomy learning. Neurosurgical training programs should tailor anatomy education according to the seniority and background of their residents. Furthermore, resources that are surgically relevant and accessible and are of high image quality are more likely to be better used.

Intermittent neck swelling: an unusual presentation of achalasia cardia.

Achalasia is a rare cause of neck swelling. We report the case of a 75-year-old woman, who presented with an intermittent, unilateral neck swelling, associated with dysphagia, weight loss and regurgitation. The patient underwent a gastroscopy and barium swallow. This confirmed a dilated oesophagus with poor motility and hold up of liquid and food residue above the gastro-oesophageal junction, thus revealing the swelling was secondary to severe achalasia. The patient was managed with botulinum toxin injections and pneumatic dilatations but the results were short lived. She is now having manometry and is being considered for a Heller myotomy or peroral oesophageal myotomy. Delayed diagnosis and treatment of achalasia can result in the development of a neck swelling, which could later cause airway compromise and subsequent mortality. Achalasia should therefore be considered in patients with an initial diagnosis of gastro-oesophageal reflux disease who do not respond to proton pump inhibitors.

Novel Variant of AVPR2 Giving Rise to X-Linked Congenital Nephrogenic Diabetes Insipidus in a 7-Month-Old Danish Boy.

Patients affected with congenital nephrogenic diabetes insipidus (CNDI) have reduced ability to concentrate urine. Early diagnosis of CNDI is important to avoid recurrent episodes of severe dehydration. We present a Danish male suffering from typical symptoms and diagnosed with CNDI at the age of 7 months. Gene sequencing of this proband and his mother revealed a novel variant in the gene encoding the antidiuretic hormone receptor (AVPR2). The variant is a deletion of nucleotide c.151 in exon 2 of AVPR2 (GenBank NM_000054.4:c.151del). This 1bp deletion is predicted to cause a frameshift that results in tryptophan replacing valine at position 51 in AVPR2 and a premature stop codon three codons downstream (p.Val51Trpfs*3) likely resulting in faulty expression of the receptor. Identification of disease-causing variants such as the one described here contributes to precise diagnosis, especially in carriers and newborns, thus preventing the long-term physical and intellectual disability observed in some CNDI-patients.

Retroperitoneal seminoma, a rare cause of testicular pain.

Extragonadal retroperitoneal seminomas are a rare cause of testicular pain in males. We report the case of a 46-year-old man, who presented with right-sided testicular pain, clinically mimicking testicular torsion. The patient underwent a scrotal exploration, which revealed normal testes. He went on to have a contrast-enhanced CT abdomen and pelvis, which revealed a 55 mm para-aortic mass, displacing the duodenum and inferior vena cava, with an adjacent 22 mm lymph node. Histological analysis revealed that it was a seminoma.

A Platform for Mechano(-Electrical) Characterization of Free-Standing Micron-Sized Structures and Interconnects.

A device for studying the mechanical and electrical behavior of free-standing micro-fabricated metal structures, subjected to a very large deformation, is presented in this paper. The free-standing structures are intended to serve as interconnects in high-density, highly stretchable electronic circuits. For an easy, damage-free handling and mounting of these free-standing structures, the device is designed to be fabricated as a single chip/unit that is separated into two independently movable parts after it is fixed in the tensile test stage. Furthermore, the fabrication method allows for test structures of different geometries to be easily fabricated on the same substrate. The utility of the device has been demonstrated by stretching the free-standing interconnect structures in excess of 1000% while simultaneously measuring their electrical resistance. Important design considerations and encountered processing challenges and their solutions are discussed in this paper.

Establishing the need for clinical follow-up after emergency appendicectomy in the modern era: Retrospective case series of 145 patients.

INTRODUCTION: Emergency appendicectomy (EA) is a commonly performed operation, with an increasing number of EAs being performed as day-case. The aim of this study is to establish if there is a need for post-operative follow-up and if this could prevent adverse outcomes. METHODS: A retrospective analysis of patients who underwent EA at multiple centres over a six-month period was undertaken. They were contacted by telephone and a standardised questionnaire was used to ascertain post-operative outcomes, including duration of analgesia use, duration before return to normal daily activity (ADLs), surgical site infection rates (SSI) and rates of re-presentation to medical services. Patients were stratified into those who underwent laparoscopic versus open appendicectomy, smokers versus non-smokers, and body mass index (BMI). RESULTS: A total of 145 patients were included in the study. Patients undergoing open surgery (vs. laparoscopic surgery) required analgesia for significantly longer periods, with a significantly longer return to ADLs. Smokers, when compared to non-smokers experienced a significantly longer return to work/school; and significantly higher risk of SSI and re-presenting to accident & emergency; as did patients with a BMI >30 when compared to those with a BMI <30. CONCLUSION: Most patients do not need formal outpatient assessment after EA. However, there is clearly a subset of higher risk patients who may benefit from this - patients who are smokers or obese. They have prolonged recovery times, and are at greater risk of SSI. Earlier surgical outpatient follow-up of these patients could prevent adverse outcomes.

Cataract surgery outcomes in pediatric patients with systemic comorbidities

Purpose: The aim of the study was to evaluate the outcomes of cataract surgery in patients of the pediatric age group with systemic comorbidities. Methods: Medical records of 54 eyes (30 patients) of the pediatric age group with systemic comorbidities who had undergone cataract surgery in a tertiary?care center were reviewed. The following parameters were recorded: systemic comorbidity; toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV (TORCH) profile, best spectacle?corrected visual acuity (BSCVA), strabismus, nystagmus, and cataract morphology. Results: Thirty patients with a mean age of 55 months (9 months–14 years) were included. On average, every child was seen by three physicians, and the mean duration between the first visit to a physician and presentation to our center was 2.23 ± 0.67 years. The various causes for delay in referral include multiple referrals due to a lack of general anesthesia services in 78% of cases, a long waiting list at the referral hospital in 35% of cases, and a lack of awareness at the primary?care physician level in 50% of cases. The mean BSCVA at presentation was 1.4 logMAR (0.3 to 3 logMAR). The most common cataract morphology was that of zonular cataract (31.48%; 17/54). Strabismus and abnormal eye movements were observed in 27.7% (15/54) and 33.3% (18/54) of eyes, respectively. Various systemic associations were periventricular leukomalacia (12/30), Down’s syndrome (6/30), seizure disorder (6/30), cardiac valvular anomalies (6/30), Marfan’s syndrome (4/30), hypothyroidism (4/30), rubella (3/20), cytomegalovirus (3/20), cerebral palsy (2/30), nephrotic syndrome (2/30), Type 1 diabetes mellitus (1/30), microcephaly (1/30), cryptogenic West syndrome (1/30), congenital rubella syndrome (1/30), and Tourette syndrome (1/30). The mean postoperative corrected distance visual acuity (CDVA) at 2?year follow?up improved to 1.0 logMAR (0 to 3 logMAR). No postoperative complications were reported at the final follow?up. Around 70% of the parents reported improvement in their child’s psychomotor skills. Conclusion: Intellectually impaired pediatric patients with cataract should be operated upon whenever there is a presence of infrastructure, and unnecessary delay in surgery should be avoided by referring the patient to higher centers. Even though objective improvement in visual acuity was suboptimal, there was definitely an improvement in the psychomotor skills of the patients.

Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes Insipidus.

Early diagnosis and treatment of congenital nephrogenic diabetes insipidus (CNDI) are essential due to the risk of intellectual disability caused by repeated episodes of dehydration and rapid rehydration. Timely genetic testing for disease-causing variants in the arginine vasopressin receptor 2 (AVPR2) gene is possible in at-risk newborns with a known family history of X-linked CNDI. In this study, a Swedish male with no family history was diagnosed with CNDI at 6 months of age during an episode of gastroenteritis. We analyzed the coding regions of AVPR2 by PCR and direct DNA sequencing and identified an 80-bp duplication in exon 2 (GenBank NM_000054.4; c.800_879dup) in the proband. This variant leads to a frameshift and introduces a stop codon four codons downstream (p.Ala294Profs*4). The variant gene product either succumbs to nonsense-mediated decay or is translated to a truncated nonfunctional vasopressin V2 receptor. This variant was absent in four unaffected family members, including his parents, as well as in 100 alleles from healthy controls, and is thus considered a novel de novo disease-causing variant. Identification of the disease-causing variant facilitated precise diagnosis of CNDI in the proband. Furthermore, it allows future genetic counseling in the family. This case study highlights the importance of genetic testing in sporadic infant cases with CNDI that can occur due to de novo variants in AVPR2 or several generations of female transmission of the disease-causing variant.

Ultra-Stretchable Interconnects for High-Density Stretchable Electronics.

The exciting field of stretchable electronics (SE) promises numerous novel applications, particularly in-body and medical diagnostics devices. However, future advanced SE miniature devices will require high-density, extremely stretchable interconnects with micron-scale footprints, which calls for proven standardized (complementary metal-oxide semiconductor (CMOS)-type) process recipes using bulk integrated circuit (IC) microfabrication tools and fine-pitch photolithography patterning. Here, we address this combined challenge of microfabrication with extreme stretchability for high-density SE devices by introducing CMOS-enabled, free-standing, miniaturized interconnect structures that fully exploit their 3D kinematic freedom through an interplay of buckling, torsion, and bending to maximize stretchability. Integration with standard CMOS-type batch processing is assured by utilizing the Flex-to-Rigid (F2R) post-processing technology to make the back-end-of-line interconnect structures free-standing, thus enabling the routine microfabrication of highly-stretchable interconnects. The performance and reproducibility of these free-standing structures is promising: an elastic stretch beyond 2000% and ultimate (plastic) stretch beyond 3000%, with <0.3% resistance change, and >10 million cycles at 1000% stretch with <1% resistance change. This generic technology provides a new route to exciting highly-stretchable miniature devices.

New Xanthone from the roots of Swertia cordata (G. Don) Clarke.

The chloroform extract of Swertia cordata (G. Don) roots was subjected to column chromatography, afforded two (one new and one known) xanthones. Both the compounds were isolated for the first time from S. cordata. The structures of the isolated compounds were established on the basis of melting point,1D (1H NMR & 13C NMR) and 2D (1H 1H COSY, HSQC & HMBC) NMR spectroscopy, in addition to high-resolution mass spectrometry.

Omental torsion, a rare cause of acute abdomen.

Omental torsion is a rare cause of acute abdominal pain. We report a case of omental torsion in a 7-year-old girl, who presented with right iliac fossa pain. The patient underwent an open appendicectomy, during which a normal appendix was identified and a diagnosis of omental torsion was made. The affected segment of omentum was resected along with the appendix. The patient made an uncomplicated recovery and was discharged on day 1 postoperatively. A normal appendix in the presence of omental torsion is found in 0.1% of all appendicectomies in children. We suggest routine visualisation of the omentum in the presence of a normal appendix during appendicectomy.