bluuebunny/crossref_metadata_2025 huggingface dataset:
Penile reconstruction
Authors: Garaffa Giulio , Ralph David J.
Published: September 2021

Penile reconstructive surgery which aims to restore adequate appearance and genitourinary function poses surgical challenges, since no tissue in the body represents an ideal substitute for the unique tunica albuginea and corpora cavernosa.
Modification of the facial skeleton in aesthetic facial surgery
Authors: Johnson Paul , Tighe David
Published: September 2021

The facial bones form the foundation of the face and provide support for the overlying soft tissues. Changing their structure can have profound effects on facial appearance. Procedures may involve augmentation, bone reduction by contouring, or repositioning of bones by means of osteotomies. Each of these techniques can be used to improve facial appearance.
Treatment of small breasts and inverted nipples
Authors: Grob Marion , Smock Elliott
Published: September 2021

Augmentation mammoplasty is one of the most popular aesthetic surgical procedures in the world and the number of cases performed continues to increase yearly. This chapter presents a comprehensive review of this topic which includes implant selection, surgical approaches, management of complications, and some of the pitfalls associated with this popular procedure. The chapter also covers the classification and treatment of inverted nipples.
Abdominal wall anatomy
Authors: Wilson Jones Nicholas
Published: September 2021

An understanding of the abdominal wall anatomy is essential for the aesthetic and reconstructive surgeon. Recent advances in imaging modalities have allowed us to further evaluate the abdominal wall. This chapter describes the complex adipofascial, muscular, vascular, and lymphatic anatomy relevant to all surgeons operating on the abdominal wall.
Factitious injury and related conditions
Authors: Kay Simon , Bellew Maggie
Published: September 2021

Some patients consciously or unconsciously generate their own symptoms or physical injuries. Excluding deliberate self-harm (acknowledged by the patient), the remaining presentations can be categorized as somatoform disorders, factitious disorders (including Munchausen’s syndrome and Munchausen’s syndrome by proxy), and malingering. The distinction between these disorders is important for the plastic surgeon who may have the first opportunity to diagnose them.
Legal aspects of consent to treatment and the nature of malpractice claims in the United Kingdom
Authors: Ashley Mark
Published: September 2021

The UK law on consent to medical treatment is derived from statutes (acts of parliament and their subordinate statutory instruments) and case law which develops as individual cases are decided by the courts. Regard must also be had to guidance published by the General Medical Council, which all UK-registered medical practitioners are expected to follow. Further detailed guidance on consent is provided by the Royal College of Surgeons.
Soft tissue infections of the hand and upper limb
Authors: Collier Sophie , Jemec Barbara
Published: September 2021

This chapter offers a comprehensive overview of the management of soft tissue infections of the upper limb, including operative control, antibiotic prophylaxis, and treatment in acute, chronic, and atypical cases.
Soft tissue reconstruction of the hand
Authors: Elliot David
Published: September 2021

This chapter describes the requirements and options available for reconstruction of the various defects encountered in the hand according to location within the fingers, thumb, and the hand itself.
Microsurgical reconstruction of the upper limb
Authors: Hamilton Alex E.
Published: September 2021

This chapter describes the microsurgical options for reconstruction of the hand, including replantation of amputated parts, nerve reconstruction, and free tissue transfer for reconstruction. The various free flap options for reconstruction of skin, soft tissue, and bone defects including the reconstruction of digits with toe transfer, are discussed.
Soft tissue inflammatory disorders of the hand
Authors: Akhtar Sohail
Published: September 2021

Soft tissues are an important interface between the tendons and bones of the hand. This interface provides both physical and biological functions by facilitating smooth tendon excursion, tendon healing, and tendon and joint stability. Disease of these soft tissues results in pain, swelling, and loss of function, and can be due to systemic conditions or local factors. These conditions include disease of the tendon sheath, disease of the tendon synovium, and diseases of tendon attachments. Inflammation was considered a universal hallmark in these conditions but recent evidence suggests that this is not true for all such conditions, whose treatment has consequently been modified. This knowledge has also caused reflection on the nomenclature used to describe these conditions and has brought clarity to the traditionally used terminology such as tenosynovitis.
Tendon transfers in the hand and wrist
Authors: Hernon Cath
Published: September 2021

This chapter discusses the general principles and indications for tendon transfers in the hand and wrist. The main functional deficits requiring tendon transfers in the upper limb result from peripheral nerve injury. Clinical assessment for each specific nerve deficit and reconstructive options are discussed. The evolution of various reconstructive strategies is reviewed and the rationale for the commonly used techniques is described. Brief descriptions of some techniques are included.
Pain syndromes
Authors: Elliot David
Published: September 2021

Pain syndromes in the upper limb related to peripheral nerve injury are often debilitating and difficult to treat. This chapter describes a systematic approach to the problems of painful end-neuromas and neuromas-in-continuity and the other phenomena associated with nerve injury.
Soft tissue swellings of the hand and upper limb
Authors: Devaraj Vikram
Published: September 2021

There is a broad range of soft tissue swellings in the hand, and most are benign lesions. Depending on their nature, they can be managed non-surgically or by excision. Malignant lesions are rare and careful assessment of the patient at presentation with appropriate investigation will distinguish these lesions which may require a multimodal approach to treatment.
Systemic disorders reflected in the hand
Authors: Watson Stewart
Published: September 2021

Clinical examination of the hand can reveal a broader diagnosis with manifestations of many systemic conditions evident to the experienced clinician. The features of these conditions are discussed in this chapter.
Assessment of patients with craniosynostosis
Authors: White Nicholas
Published: September 2021

The term craniosynostosis denotes the pathological partial or complete absence of one or more cranial sutures which manifests as abnormal skull growth. Although it is often referred to as premature fusion this is misleading as only the metopic suture fuses in the normal physiological state. The remaining sutures change and mature in macroscopic and microscopic form during growth but remain present. This chapter discusses the assessment of patients with craniosynostosis.
Non-syndromic craniosynostosis
Authors: Duncan Christian , Nishikawa Hiroshi
Published: September 2021

Craniosynostosis is defined as the premature fusion of a skull suture and has an incidence of approximately 1:2000 live births. Historically, craniosynostosis was subdivided into primary and secondary synostosis. Further subclassifications included syndromic/non-syndromic and single/multisuture. Multisuture synostoses also give rise to characteristic head shapes, which, with experience, are readily identifiable by experienced clinicians using clinical examination alone. While in the past, single-suture craniosynostosis was classified as ‘non-syndromic’, advances in genetic analysis has shown that this may not be the case in a proportion of these cases, just as some multisuture presentations may also be non-syndromic. This particularly applies to unicoronal craniosynostosis along with some metopic and bicoronal synostosis. Given the higher rate of syndromic association in these patients, along with the tendency to require late surgery for facial scoliosis in unicoronal and unilambdoid patients, this cohort should be regarded as a more complex subset.
Orofacial clefts
Authors: FitzPatrick David R.
Published: September 2021

Orofacial clefting is an umbrella term for common human malformations. The most common of these malformations result from failure of tissue fusion events during formation of the embryonic face. Single-gene causes of orofacial clefting are rare and often associated with other clinical features in the form of a recognizable syndromal diagnosis. Isolated orofacial clefting is most likely caused by gene–environment interactions but the exact nature of these interactions is not yet known
Outcome assessment in cleft lip and palate surgery
Authors: Swan Marc C. , Harrison Conrad J. , Goodacre Tim E.E.
Published: September 2021

Outcome assessment for cleft management is complex due to the diverse elements of function affected by the condition, and the variation in effect on patients over time. Methods of assessment are broadly separated into objectively measurable variables that can be independently validated, and patient-reported measures that are necessarily more subjective. Validated tools to evaluate outcomes are now widely adopted for speech and facial growth, with other areas of outcome presenting greater problems in development of suitable measures. In recent years, the emphasis of outcome evaluation has turned towards greater reliance on patient-reported measures that require extensive preliminary research to develop if a high degree of validity is to be ensured. Existing outcome measures that are widely used are described in this chapter, along with a perspective for future trends and a forthcoming internationally applicable tool for comparative studies (ICHOM).
Secondary surgery in cleft lip and palate
Authors: Hodgkinson Peter D.
Published: September 2021

Secondary surgery in patients with cleft lip and palate should be undertaken within a cleft multidisciplinary team where such expertise is available. A clinical psychologist can identify issues related (or unrelated) to the cleft and aid in establishing appropriate patient expectations if surgery is contemplated. The requirements of patients considering secondary cleft surgery are more similar to the needs of patients undergoing primary surgery than they are to other non-cleft facial surgery patients. Secondary surgical procedures appropriate to cleft lip and palate patients include revisional lip surgery, adjunctive alveolar or maxillary surgery, orthognathic surgery, revisional nasal surgery, and adjunctive facial procedures. These procedures tend to be performed once facial growth is complete and may need to be coordinated with other interventions, including orthodontics and speech assessment. Surgical procedures should be correctly sequenced and a long-term plan made in conjunction with the patient.
The head and neck multidisciplinary team
Authors: Sørensen Kristian
Published: September 2021

The head and neck multidisciplinary team (MDT) is a multiprofessional group that provides comprehensive care for patients with head and neck cancers. The MDTs were created to standardize care given to head and neck patients. Local, regional, and national guidelines are followed by the MDTs to ensure optimum care throughout the whole disease process. Outcome measures are recorded and serve as benchmarks to compare care delivered to patients. MDTs contribute to clinical research and to national audits, as well as serving as the interface between specialist clinical services and primary care. A lead clinician is responsible for each MDT’s performance and compliance with established standards.
Assessment and management of metastatic neck disease
Authors: Paleri Vinidh , Ragbir Maniram
Published: September 2021

Tumour spread to the neck can occur from any primary sites that can harbour squamous cell carcinoma (SCC) in the upper aerodigestive tract (UADT) mucosa. This can also happen with other histological subtypes and from primary sites in the parotid and thyroid gland. Thus, the assessment of the neck should form an integral part of the clinical examination, imaging, and decision-making process prior to deciding treatment of the primary tumour. Given the propensity of these tumours to spread to the lymph nodes and given that the treatment algorithms used to manage lymph nodes in the neck are similar to those options available for the primary site, neck status often influences the choice of treatment. This chapter outlines the assessment and management of the metastatic neck node from an SCC of the UADT. To ensure uniformity in describing and communicating information about neck disease, the neck is divided into six levels, as recommended by the American Head and Neck Society and the American Academy of Otolaryngology–Head and Neck Surgery.
Cheek reconstruction
Authors: Potter Matthew
Published: September 2021

This chapter will give the reader an understanding on how to reconstruct the cheek. It breaks down the topic into the anatomy, the aesthetic principles behind reconstruction, and the flaps commonly used to reconstruct defects of the cheek of any size or depth.
Nasal reconstruction
Authors: Kernohan Michael D. , Thornbury Kelly
Published: September 2021

Reconstruction of nasal skin is one of the earliest recorded procedures of what is now referred to as the discipline of reconstructive plastic surgery. In the ancient Hindu Sanskrit text, ‘Sushruta Samhita’ (600–700 bc) the forehead rhinoplasty is described and later the Italian surgeon Tagliacozzi (1597) performed nasal reconstruction with skin pedicled from the upper arm. These early procedures treated the defects left by the ancient punishment of nasal amputation. Sir Harold Gillies and colleagues reinvigorated the art of plastic surgery after the First World War and provided the sound principles of reconstruction that are followed to this day. In more modern times, the refinement of this surgical technique has advanced considerably due to the work and publications of Dr Gary Burget and Dr Frederick Menick. They have greatly flattened the learning curve and finesse of the paramedian forehead flap and associated procedures.
Reconstruction of the pharynx
Authors: Pollock Jonathan , Ragbir Maniram
Published: September 2021

Reconstruction of the pharynx and cervical oesophagus represents a significant challenge for the plastic surgeon due to the complex functions and anatomical structures to be restored. Malignancy is the most common cause of pharyngeal defects, and this patient cohort has a generally poor prognosis due to the tendency to present late with advanced disease. While tumours of the hypopharynx make up only 5% of all head and neck cancers, the surgical management of laryngeal and upper oesophageal malignancy frequently involves the need to reconstruct or reinforce the pharynx. Reconstruction for these patients is further complicated by medical comorbidity, synchronous malignancy, and the patients’ poor nutritional state. With the move in recent years to chemoradiotherapy protocols for advanced disease, surgery is performed less frequently. Nevertheless, there is still a need for surgical management in both primary treatment and salvage cases following chemoradiotherapy. As survival is poor in this group, it is important that quality of life after reconstruction is considered, and hospital stay minimized. The restoration of an oral diet and intelligible speech is the priority, but there are a multitude of factors which must be considered when selecting the best reconstruction. This chapter outlines some historical methods of pharyngeal reconstruction, followed by the indications, advantages, and disadvantages of the methods in current use.
Reconstruction of the mandible and maxilla
Authors: Bryant Colonel Douglas G. , Jones Alex P. , Ragbir Maniram
Published: September 2021

Mandibular and maxillary reconstruction is commonly required in clinical practice following major trauma or tumour resection. General principles of reconstruction should be followed: replace like with like and address functional and cosmetic deficiencies. Many reconstructive approaches are applicable to both mandibular and maxillary reconstruction and free vascularized tissue transfer is the accepted standard for both these anatomical sites with flaps such as the fibula or iliac crest. Advances in microsurgery allow high-quality, reproducible reconstructions to be performed by specialist teams. Reconstruction modality will be influenced by a range of factors such as defect site, size, and soft tissue involvement, as well as patient factors such as general health, dentition, age, and further planned treatment. Key factors to consider when reconstructing the midface and jaw include the airway, swallowing, speech, nutrition, and dental rehabilitation. These are also considered in this chapter. Computer modelling and surgical planning based on preoperative computed tomography scanning is now commonly used by many teams and this is also discussed.
Adjuvant therapy for head and neck cancers
Authors: Kelly Charles
Published: September 2021

The non-surgical management of head and neck cancer has changed over the last two decades with more emphasis given now to organ preservation and post-treatment organ function. These two concepts do not necessarily go hand in hand but preserving an organ without preserving its function is pointless. In this period, for some head and neck cancers subsites, for example, oropharynx, the treatment model has moved away from primary surgery followed by planned, adjuvant radiotherapy, to one of primary chemoradiotherapy with the objective of greater organ and function preservation. This change in management strategy may be coming under further review now, with the introduction of transoral robotic surgery (TORS), where the treatment model may revert back to primary surgery with the question raised, whether highly selective TORS followed by highly selective adjuvant radiotherapy using the newer radiation technologies and techniques with intensity-modulated radiotherapy or tomotherapy, with or without chemotherapy might optimize tumour control with minimal long-term morbidity.
Upper trunk and breast surgery after massive weight loss
Authors: Akhavani Mohammed , Soldin Mark
Published: September 2021

This chapter discusses upper trunk and breast surgery after massive weight loss in females and males.
Thigh lift
Authors: Barabás Anthony , Soldin Mark
Published: September 2021

The skin of the medial thigh is thin and inelastic, and laxity here is often the earliest sign of ageing in the thighs. The medial thigh skin is also one of the areas most affected following weight loss. The majority of skin laxity occurs at the junction of the anterior and medial thigh, where the skin tends to hang in a dependent, pleated fashion. This can interfere with walking, toileting, and various other day-to-day activities, resulting in irritation due to chaffing between the thighs. Body contouring techniques are routinely combined in stages to achieve a more harmonious result. Medial thigh lift is frequently combined with upper body lift or breast surgery, or both, whereas brachioplasty is usually combined with abdominoplasty/lower body lift. Opposing vectors of pull and excessive damage to local vascularity are thereby avoided. However, staging surgical procedures has the potential to reveal additional areas of dissatisfaction to the patient. Abdominoplasty patients often report increased dissatisfaction with the medial thighs as a consequence of this previously hidden deformity becoming visible to them postoperatively. In fact, massive weight-loss patients’ dissatisfaction with their thighs is almost as great as with the changes to their breasts in terms of their severely decreased self-esteem, sexuality, and quality of life.
The ageing breast
Authors: Hudson Donald
Published: September 2021

The breast is a subcutaneous structure which changes with age. The supporting structures of the breast include the parenchyma, fat, skin, and, most importantly, the fascial system which connects the skin to the underlying muscles via Cooper’s ligaments. Each of these components changes throughout life, changing the breast appearance as the body ages. Many factors influence the effect of ageing (genetics, smoking, weight fluctuation, pregnancy, hormone replacement therapy, etc.). The firm, full, youthful breast slowly becomes a softer and more hanging structure. The weakening of the supporting structures of the breast commonly leads to ptosis. In some patients, atrophy of the breast occurs with ageing, whereas with others, hypertrophy occurs.
Asymmetry of the breast
Authors: Ali Farida
Published: September 2021

Developmental breast asymmetry is common in women and may be associated with significant psychological distress. It may be due to deformity of the breast itself (true) or secondary to abnormalities of the underlying torso (apparent). True breast asymmetry may be congenital or acquired. This chapter gives an overview of the aetiology and classification of developmental breast asymmetry and discusses the clinical evaluation of women presenting with breast asymmetry. Congenital breast asymmetry, subdivided into hypoplastic, hyperplastic, and deformational, is discussed. The abnormalities and challenges specific to Poland syndrome and tuberous breast deformity are described. For each subdivision, the surgical techniques available to correct the deformity are reviewed. The limitations of surgery and potential outcomes are discussed.
The burnt child
Authors: Rea Suzanne , Falder Sian
Published: September 2021

Burns are a common form of trauma in children. Common mechanisms of injury include scalds from hot beverages and contact burns from household items. The physical and psychological trauma may have long-lasting effects for both child and family. Children are not just small adults; there are important anatomical and physiological differences. Paediatric burn patients have specific treatment needs that must be accounted for. Estimation of burn size, threshold for commencement of intravenous fluid resuscitation and enteral feeding, in addition to wound assessment, wound care, and treatment are all different to a similar size injury in an adult. These paediatric-specific issues are discussed in more detail. The investigation and interpretation of suspected non-accidental burn presenting to a burns unit is also outlined.
Electrical injury and burns and their management
Authors: Sainsbury David C.G. , Fish Joel
Published: September 2021

Though responsible for just 4% of burn centre admissions, electrical injuries present in a myriad of ways. From small, innocuous, partial-thickness injuries on the fingertip, to a high-voltage injury requiring amputation and complex reconstruction, the burn surgeon must be equipped with the knowledge and skill to deal with such varying injuries. This chapter describes the epidemiology of electrical injury and the pathophysiology of electrical current passing through the patient. The management of high- and low-voltage wounds is described, as is the treatment of the systemic effects of the electrical injury.
A Standardized Method for Estimating the Carbon Footprint of Disposable Minimally Invasive Surgical Devices
Authors: Misrai Vincent , Rijo Enrique , Cottenceau Jean-Baptiste , Zorn Kevin C. , Enikeev Dmitry , Elterman Dean , Bhojani Naeem , De La Taille Alexandre , Herrmann Thomas R. W. , Robert Gregoire , Pradere Benjamin
Published: September 2021

Objective:

To propose a standardized methodology for estimating the embodied carbon footprint (CF) of disposable minimally-invasive surgical devices (MISDs) and their application in new benign prostatic hyperplasia (BPH) MISDs.

Summary of Background Data:

The estimation of the CO2e emissions of disposable surgical devices is central to empowering the healthcare supply chain.

Methods:

The proposed methodology relied on a partial product lifecycle assessment and was restricted to a specific part of scope 3, which comprised the manufacturing of surgical device- and non–device-associated products (NDAPs), including packaging and user manual. The process-sum inventory method was used, which involves collecting data on all the component processes underpinning disposable MISDs. The seven latest disposable MISDs used worldwide for transurethral prostatic surgery were dismantled, and each piece was categorized, sorted into the appropriate raw material group, and weighed. The CF was estimated according to the following formula: activity data (weight of raw material) × emission factors of the corresponding raw material (kg CO2e/kg).

Results:

The total weights of disposable packaging and user manuals ranged from 0.062 to 1.013 kg. Plastic was the most common and least emissive raw material (2.38 kg CO2e/kg) identified. The estimated embodied CF of MISDs ranged from 0.07 to 3.3 kg CO2e, of which 9% to 86% was attributed to NDAPs.

Conclusions:

This study described a simple and independent calculation method for estimating the embodied CF of MISDs. Using this method, our results showed a wide discrepancy in the estimated CO2 emissions of the most recent disposable MISDs for transurethral BPH surgery. Thus, the lack of CF information should be of major concern in the development of future MISDs.
Randomized, double-blind, placebo-controlled trial of ISC 17536, an oral inhibitor of transient receptor potential ankyrin 1, in patients with painful diabetic peripheral neuropathy: impact of preserved small nerve fiber function
Authors: Jain Sunil M. , Balamurugan Ramanathan , Tandon Monika , Mozaffarian Neelufar , Gudi Girish , Salhi Yacine , Holland Robert , Freeman Roy , Baron Ralf
Published: September 2021

Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of “precision medicine” or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.
Collagenous colitis: a rare cause of chronic diarrhea
Authors: Wu Ping-Ju , Lin Chien-Chieh , Wang Jiunn-Wei
Published: September 2021

Introduction:

Collagenous colitis is a chronic inflammatory disease of the colon with a peak incidence in middle-aged adults. It is characterized by chronic diarrhea and pain from abdominal cramping, with near normal mucosa morphology under gross colonic examination by colonoscopy. Currently, the pathogenesis remains unclear but there is speculation of an association with abnormal collagen metabolism, contributing to prominent sub-epithelial matrix deposition.

Patient concerns:

A 51-year-old male patient without any underlying disease presented after experiencing watery light brown diarrhea 4–5 times per day for the past 2 months.

Diagnosis:

The diagnosis of collagenous colitis was confirmed by the pathological examination of the second colonic biopsy, which reported positive Masson's trichrome staining.

Intervention:

The patient was initially diagnosed with unspecified functional bowel disorder, but showed no clinical improvement after treatment with oral medication. Mesalamine therapy was administered after collagenous colitis was diagnosed by follow-up colonoscopy.

Outcome:

Normal bowel movement was restored in the patient after 2 weeks of mesalamine therapy.

Conclusion:

Collagenous colitis is a rare etiology of chronic diarrhea, which can only be diagnosed by pathology of colonic mucosa. Consequently, repeat colonoscopy with multiple stepwise random colonic biopsies at suspicious lesion sites or even normal-appearing mucosa should be considered in refractory chronic diarrhea patients without established diagnoses.
Prevalence and Factors Associated With Indwelling Non-Utilized (Idle) Central Vascular Access Devices Across All Age Groups
Authors: Tripathi Sandeep , Gladfelter Taylor R.
Published: September 2021

A retrospective study was conducted in a large, urban, pediatric/adult hospital to investigate the extent of idle central vascular access devices (CVADs) across all age groups and to identify factors that contribute to an in situ nonutilized CVAD. Patients who were hospitalized for >4 days between January 2015 and December 2019 were included. Implanted ports, tunneled catheters, and umbilical lines were excluded. Idle time was defined as a calendar day in which no intravenous medication was administered. A total of 6054 CVADs (59% nontunneled CVADs, 41% peripherally inserted central catheters [PICCs]; 73% adults, 27% children) were analyzed. Among these, 1263 (21%) had at least 1 idle day, with a median idle time and proportion of 3 days and 25%, respectively. Up to 51% and 64% of lines placed in infants/neonatal intensive care unit had idle time compared with 13% and 12% in adults/medical intensive care units (ICUs). The median idle time for PICCs was longer than that of nontunneled CVADs. CVADs with dwell duration greater than the median (duration for their respective departments) had 5.0 (95% CI, 4.2–5.9) odds of being idle. CVADs in the neonatal ICU had 14.2 (95% CI, 10.8–18.6) odds of having idle time compared with those in the medical ICU. This study found that 1 of every 5 CVADs had at least 1 day of idle time, with one fourth of their total dwell duration idle. CVADs with longer dwell duration, those placed in children, and PICCs were more likely to be idle.
Functional characterization of a gene cluster responsible for inositol catabolism associated with hospital-adapted isolates of Enterococcus faecium
Authors: Top Janetta , Baan Jery , Bisschop Adinda , Arredondo-Alonso Sergio , van Schaik Willem , Willems Rob J. L.
Published: September 2021

Enterococcus faecium

is a nosocomial, multidrug-resistant pathogen. Whole genome sequence studies revealed that hospital-associated

E. faecium

isolates are clustered in a separate clade A1. Here, we investigated the distribution, integration site and function of a putative iol gene cluster that encodes for myo-inositol (MI) catabolism. This iol gene cluster was found as part of an ~20 kbp genetic element (iol element), integrated in ICEEfm1 close to its integrase gene in

E. faecium

isolate E1679. Among 1644

E. faecium

isolates, ICEEfm1 was found in 789/1227 (64.3 %) clade A1 and 3/417 (0.7 %) non-clade A1 isolates. The iol element was present at a similar integration site in 180/792 (22.7 %) ICEEfm1-containing isolates. Examination of the phylogenetic tree revealed genetically closely related isolates that differed in presence/absence of ICEEfm1 and/or iol element, suggesting either independent acquisition or loss of both elements. E. faecium iol gene cluster containing isolates E1679 and E1504 were able to grow in minimal medium with only myo-inositol as carbon source, while the iolD-deficient mutant in E1504 (E1504∆iolD) lost this ability and an iol gene cluster negative recipient strain gained this ability after acquisition of ICEEfm1 by conjugation from donor strain E1679. Gene expression profiling revealed that the iol gene cluster is only expressed in the absence of other carbon sources. In an intestinal colonization mouse model the colonization ability of E1504∆iolD mutant was not affected relative to the wild-type E1504 strain. In conclusion, we describe and functionally characterise a gene cluster involved in MI catabolism that is associated with the ICEEfm1 island in hospital-associated

E. faecium

isolates. We were unable to show that this gene cluster provides a competitive advantage during gut colonisation in a mouse model. Therefore, to what extent this gene cluster contributes to the spread and ecological specialisation of ICEEfm1-carrying hospital-associated isolates remains to be investigated.
Lab-on-a-chip multiplexed electrochemical sensor enables simultaneous detection of SARS-CoV-2 RNA and host antibodies
Authors: Najjar Devora , Rainbow Joshua , Timilsina Sanjay Sharma , Jolly Pawan , de Puig Helena , Yafia Mohamed , Durr Nolan , Sallum Hani , Alter Galit , Li Jonathan Z. , Yu Xu G. , Walt David R. , Paradiso Joseph A. , Estrela Pedro , Collins James J. , Ingber Donald E.
Published: September 2021

The current COVID-19 pandemic highlights the continued need for rapid, accurate, and cost-effective point-of-care (POC) diagnostics that can accurately assess an individual’s infection and immunity status for SARS-CoV-2. As the virus continues to spread and vaccines become more widely available, detecting viral RNA and serological biomarkers can provide critical insights into the status of infectious, previously infectious, and vaccinated individuals over time. Here, we describe an integrated, low-cost, 3D printed, lab-on-a-chip device that extracts, concentrates, and amplifies viral RNA from unprocessed patient saliva and simultaneously detects RNA and multiple host anti-SARS-CoV-2 antibodies via multiplexed electrochemical (EC) outputs in two hours. The EC sensor platform enables single-molecule CRISPR/Cas-based molecular detection of SARS-CoV-2 viral RNA as well as serological detection of antibodies against the three immunodominant SARS-CoV-2 viral antigens. This study demonstrates that microfluidic EC sensors can enable multiplexed POC diagnostics that perform on par with traditional laboratory-based techniques, enabling cheaper and more widespread monitoring of infection and immunity over time.
COVID-19 mortality in children and young people in Mexico
Authors: Stern Dalia , de la Garza Eduardo Arias , García-Romero María Teresa , Lajous Martin
Published: September 2021

Objective

To estimate COVID-19 and pre-pandemic low respiratory infection (LRI) mortality in children and young people in Mexico.

Material and methods

We estimated the percentage of total mortality attributable to COVID-19 (95% confidence intervals; 95%CI) and corresponding estimates for pre-pandemic LRI mortality.

Results

In 2019, LRIs represented 8.6% (95%CI 8.3, 8.9) of deaths in children 0-9 years and 2.0% (95%CI 1.8, 2.3) in those aged 10-19 years. In 2020, corresponding estimates for COVID-19 were 4.4% (95%CI 4.1, 4.6) and 3.7% (95%CI 3.4, 4.1).

Conclusions

Relative to LRI, COVID-19 may be exerting considerable mortality burden, particularly in older children and adolescents.
Iron deficiency in Women of Childbearing Age with Self-reported Oral Iron Gastrointestinal Intolerance and Management with an oral Iron-Whey-Protein Formulation
Authors: Gilmer JGF , Ryan Fiona , Seoighe Anna , Santos-Martinez Maria Jose , Ryan Cristin , Ledwidge Mark
Published: September 2021

Background

Intolerance to oral iron is thought to result in poor adherence and persistence of nutritional deficit amongst women of childbearing age, however few studies have evaluated oral iron intolerance, iron deficiency and anaemia in this setting. Iron-whey protein microspheres (IWP) could help.

Methods

We documented self-reported oral iron gastrointestinal intolerance, ferritin and haemoglobin levels in a screening study of women of childbearing age. Following a washout period of 16 days, we randomised 59 of these women with iron deficiency, stratified according to the presence of anaemia, to three doses of IWP: (14mg daily, 25mg daily and 50mg daily). We excluded those with established gastrointestinal disease, potential allergy to whey protein and severe anaemia. The primary endpoint was persistence and adherence (>80% based on pill-counts). Secondary endpoints included changes in self-reported oral iron gastrointestinal intolerance, gastro-intestinal symptom rating scale (GSRS), serum iron, serum ferritin, transferrin saturation and haemoglobin levels.

Results

A total of 128 (62.7%) of the participants had low iron stores (ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin <12 µg/L) and 33 (16.2%) had iron deficiency anaemia. Amongst 59 women who participated in the prospective study, 48 (81.4%) were classified as adherent/persistent with therapy using IWP compared to 12 (20.3%) taking the prior oral iron p<0.0001. These patients also showed significantly fewer reports of gastrointestinal intolerance with IWP (0.59 ± 0.91) and lower GSRS scores (6.2 ± 7.5) compared to the previous oral iron product (3.98 ± 2.22, and 15.6 ± 9.7 respectively, both P<0.0001). There were no differences in adherence, self-reported adverse GI effects and GSRS between the dose groups during the study. Serum iron levels increased across the whole cohort from 11.3 ± 7.4 μmol/L to 20.5± 11.0 μmol/L (P<0.0001), transferrin saturation levels increased from 18.4 ± 13.3 % to 33.6 ± 17.6 % (P<0.0001) and median ferritin levels overall increased from 8.00 [IQR 6.00;13.0] to 15.5 [IQR 9.00;24.2] µg/L at 12 weeks (P=0.0002). Haemoglobin levels increased from 11.36 g/dL (95%CI 10.95 to 11.77) to 12.40 g/dL (95%CI 12.03 to 12.76, P=0.0007) in patients with anaemia and were normalised in most patients taking 50mg IWP daily.

Conclusions

Low iron, iron deficiency and anaemia are common in women of childbearing age with a history of intolerance to oral iron. Patients with low iron (ferritin < 30 µg/L) and moderate to severe iron deficiency (ferritin <12 µg/L) have similar impairment of energy. IWP can improve self-reported oral iron adherence and tolerability as well as iron stores, haemoglobin and tiredness in these women.
A transnational and transregional study of the impact and effectiveness of social distancing for COVID-19 mitigation
Authors: Rocha Filho Tarcísio M. , Moret Marcelo A. , Mendes José F. F.
Published: September 2021

We present an analysis of the relationship between SARS-CoV-2 infection rates and a social distancing metric from data for all the states and most populous cities in the United States and Brazil, all the 22 European Economic Community countries and the United Kingdom. We discuss why the infection rate, instead of the effective reproduction number or growth rate of cases, is a proper choice to perform this analysis when considering a wide span of time. We obtain a strong Spearman’s rank order correlation between the social distancing metric and the infection rate in each locality. We show that mask mandates increase the values of Spearman’s correlation in the United States, where a mandate was adopted. We also obtain an explicit numerical relation between the infection rate and the social distancing metric defined in the present work.
T1DMicro: A Clinical Risk Calculator for Type 1 Diabetes Related Microvascular Complications
Authors: Tran Paul Minh Huy , Kim Eileen , Tran Lynn Kim Hoang , Khaled bin Satter , Zhi Wenbo , Bai Shan , Hopkins Diane , Gardiner Melissa , Bryant Jennifer , Bernard Risa , Morgan John , Bode Bruce , Reed John Chip , She Jin-Xiong , Purohit Sharad
Published: September 2021

Development of complications in type-1 diabetes patients can be reduced by modifying risk factors. We used a cross-sectional cohort of 1646 patients diagnosed with type 1 diabetes (T1D) to develop a clinical risk score for diabetic peripheral neuropathy (DPN), autonomic neuropathy (AN), retinopathy (DR), and nephropathy (DN). Of these patients, 199 (12.1%) had DPN, 63 (3.8%) had AN, 244 (14.9%) had DR, and 88 (5.4%) had DN. We selected five variables to include in each of the four microvascular complications risk models: age, age of T1D diagnosis, duration of T1D, and average systolic blood pressure and HbA1C over the last three clinic visits. These variables were selected for their strong evidence of association with diabetic complications in the literature and because they are modifiable risk factors. We found the optimism-corrected R2 and Harrell’s C statistic were 0.39 and 0.87 for DPN, 0.24 and 0.86 for AN, 0.49 and 0.91 for DR, and 0.22 and 0.83 for DN respectively.

This tool (https://ptran25.shinyapps.io/Diabetic_Peripheral_Neuropathy_Risk) was built to help inform patients of their current risk of microvascular complications and to motivate patients to control their HbA1c and systolic blood pressure in order to reduce their risk of these complications.
Structure and ion-release mechanism of PIB-4-type ATPases
Authors: Grønberg Christina , Hu Qiaoxia , Mahato Dhani Ram , Longhin Elena , Salustros Nina , Duelli Annette , Eriksson Jonas , Rao Komal Umashankar , Henderson Domhnall Iain , Meloni Gabriele , Andersson Magnus , Croll Tristan , Godaly Gabriela , Wang Kaituo , Gourdon Pontus
Published: September 2021

Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here we present structures and complementary functional analyses of an archetypal PIB-4-ATPases, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy metal binding domains, and provides fundamentally new insights into the mechanism and diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release, and as an internal counter ion, of an invariant, central histidine. We also establish that the turn-over of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in e.g. drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
COVID-19 vaccination did not improve employee mental health: A prospective study in an early phase of vaccination in Japan
Authors: Sasaki Natsu , Kuroda Reiko , Tsuno Kanami , Imamura Kotaro , Kawakami Norito
Published: September 2021

The effect of the COVID-19 vaccination as an individual-based preventive measure on mental health is largely unclear in the literature. The authors report a preliminary finding on whether vaccination effectively improves mental health among employees in Japan based on a prospective study (E-COCO-J). Of the total sample (N=948), 105 (11.1%) were vaccinated at least once at the follow-up survey (June 2021). There was no significant effect of vaccination on the change of psychological distress at baseline (February 2021) and follow-up (June 2021), after adjusting for gender, age, marital status, education, chronic disease, company size, industry, and occupation (healthcare workers or non-HCWs). Providing continuous mental health care for employees is important in an early vaccination phase.
Monitoring populations at increased risk for SARS-CoV-2 infection in the community
Authors: Pritchard Emma , Jones Joel , Vihta Karina , Stoesser Nicole , Matthews Philippa C. , Eyre David W. , House Thomas , Bell John I , Newton John N , Farrar Jeremy , Crook Derrick , Hopkins Susan , Cook Duncan , Rourke Emma , Studley Ruth , Diamond Ian , Peto Tim , Pouwels Koen B. , Walker A. Sarah ,   the COVID-19 Infection Survey Team
Published: September 2021

Background

The COVID-19 pandemic is rapidly evolving, with emerging variants and fluctuating control policies. Real-time population screening and identification of groups in whom positivity is highest could help monitor spread and inform public health messaging and strategy.

Methods

To develop a real-time screening process, we included results from nose and throat swabs and questionnaires taken 19 July 2020-17 July 2021 in the UK’s national COVID-19 Infection Survey. Fortnightly, associations between SARS-CoV-2 positivity and 60 demographic and behavioural characteristics were estimated using logistic regression models adjusted for potential confounders, considering multiple testing, collinearity, and reverse causality.

Findings

Of 4,091,537 RT-PCR results from 482,677 individuals, 29,903 (0·73%) were positive. As positivity rose September-November 2020, rates were independently higher in younger ages, and those living in Northern England, major urban conurbations, more deprived areas, and larger households. Rates were also higher in those returning from abroad, and working in healthcare or outside of home. When positivity peaked December 2020-January 2021 (Alpha), high positivity shifted to southern geographical regions. With national vaccine roll-out from December 2020, positivity reduced in vaccinated individuals. Associations attenuated as rates decreased between February-May 2021. Rising positivity rates in June-July 2021 (Delta) were independently higher in younger, male, and unvaccinated groups. Few factors were consistently associated with positivity. 25/45 (56%) confirmed associations would have been detected later using 28-day rather than 14-day periods.

Interpretation

Population-level demographic and behavioural surveillance can be a valuable tool in identifying the varying characteristics driving current SARS-CoV-2 positivity, allowing monitoring to inform public health policy.

Funding

Department of Health and Social Care (UK), Welsh Government, Department of Health (on behalf of the Northern Ireland Government), Scottish Government, National Institute for Health Research.
The pitfalls of inferring virus-virus interactions from co-detection prevalence data: Application to influenza and SARS-CoV-2
Authors: de Cellès Matthieu Domenech , Goult Elizabeth , Casalegno Jean-Sébastien , Kramer Sarah
Published: September 2021

There is growing experimental evidence that many respiratory viruses—including influenza and SARS-CoV-2—can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio—defined as the ratio of co-infection prevalence to the product of single-infection prevalences—should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two respiratory viruses causing seasonal epidemics. By focusing on the pair influenza–SARS-CoV-2, we first demonstrate that the prevalence ratio systematically under-estimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection—such as a high reproduction number or a short infectious period—that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.