Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.

OBJECTIVE: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. SUMMARY BACKGROUND DATA: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. METHODS: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. RESULTS: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. CONCLUSION: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.

Appendicitis-related acute referrals to Children's Health Ireland from Non-Specialist Paediatric Surgical Centres.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Eighty percent of paediatric appendicectomies are performed by adult general surgeons on an annual basis. The remaining 20% are performed at Children's Health Ireland (CHI) centres. Occasionally patients are transferred from Non-Specialist Paediatric Surgical Centres (NSPSC) for specialised pre-operative or post-operative care. AIM: To assess the rates of and characterise appendicitis-related referrals to CHI at Crumlin from NSPSC. METHODS: A retrospective review of all appendicitis-related transfers to CHI at Crumlin between January 2020 and December 2021 was performed. Data relating to indications for transfer, referring hospital level, patient demographics, management, type of surgery, length of stay (LOS), and radiological studies were collected and analysed. RESULTS: Seventy-two patients were transferred to CHI at Crumlin over the 2-year period. A total of 60.9% were male, mean age 9 ± 4.3 years, mean LOS 6.0 ± 2.2 days (range 1-30 days). Nineteen percent were under 5 years of age. Seventy-three percent were transferred from level 4 centres. Ninety-seven percent were transferred pre-operatively, 25% of those transferred pre-operatively had imaging in CHI confirming appendicitis. Fifty-five percent (40/72) of patients had pre-operative imaging performed. A total of 37.5% (15/40) confirmed complicated appendicitis. Twenty percent (8/40) underwent both ultrasound and computerised tomography (CT) at the referring centre. A total of 2.7% (2/72) were transferred with known co-morbidities. Ninety-two percent (66/72) underwent appendicectomy. Eight percent (6/72) were managed non-operatively (NOM) - 2 failed NOM, 2 underwent interval appendicectomy. Of those managed operatively, 76% (50/66) underwent laparoscopic appendicectomy, and 24% (16/66) were performed open. CONCLUSION: The majority of paediatric appendicectomies are performed at Non-Specialist Paediatric Surgical Centres. It is vital to maintain this working relationship so that specialist paediatric centres are available to provide care to complex paediatric patients.

Single, Recurrent, Synchronous, and Metachronous Periprosthetic Joint Infections in Patients With Multiple Hip and Knee Arthroplasties.

BACKGROUND: The rate for periprosthetic joint infection (PJI) exceeds 1% for primary arthroplasties. Over 30% of patients who have a primary arthroplasty require an additional arthroplasty, and the impact of PJI on this population is understudied. Our objective was to assess the prevalence of recurrent, synchronous, and metachronous PJI in patients who had multiple arthroplasties and to identify risk factors for a subsequent PJI. METHODS: We identified 337 patients who had multiple arthroplasties and at least 1 PJI that presented between 2003 and 2021. The mean follow-up after revision arthroplasty was 3 years (range, 0 to 17.2). Patients who had multiple infected prostheses were categorized as synchronous (ie, presenting at the same time as the initial infection) or metachronous (ie, presenting at a different time as the initial infection). The PJI diagnosis was made using the MusculoSkeletal Infection Society (MSIS) criteria. RESULTS: There were 39 (12%) patients who experienced recurrent PJI in the same joint, while 31 (9%) patients developed PJI in another joint. Positive blood cultures were more likely in the second joint PJI (48%) compared to recurrent PJI (23%) or a single PJI (15%, P < .001). Synchronous PJI represented 42% of the second joint PJI cases (n = 13), while metachronous PJI represented 58% (n = 18). Tobacco users had 75% higher odds of metachronous PJI (odds ratio 1.75, 95% confidence interval: 1.1-2.9, P = .041). CONCLUSION: Over 20% of the patients with multiple arthroplasties and a single PJI will develop a subsequent PJI in another arthroplasty with 12% recurring in the initial arthroplasty and nearly 10% ocurring in another arthroplasty. Particular caution should be taken in patients who use tobacco, have bacteremia, or have Staphylococcus aureus isolation at time of their initial PJI. Optimizing the management of this high-risk patient population is necessary to reduce the additional burden of subsequent PJI. LEVEL OF EVIDENCE: Prognostic Level IV.

Lost in translation: Telephone referrals to a tertiary neurology referral centre.

BACKGROUND: Cork University Hospital acts as the tertiary referral centre for the HSE southern area, with a catchment population of 1.2 million [1]. The neurology registrars receive telephone consultations from hospitals and primary care practices in the region. While there have been a number of studies examining inpatient neurology consultations in Irish hospitals [2-6], there is a paucity of data examining the support provided by tertiary referral centres to other acute hospitals and primary care centres in their region. AIMS: The aim of this study is to define the workload of the neurology registrar with respect to telephone consultations and to examine the quality of these referrals. METHODS: All calls received from the 19th of October 2021 to the 25th of February 2022 were logged by the receiving registrar. Information collected pertained to the nature of the consult and completeness of the referral. RESULTS: The average volume of calls during the study period was six per week. The median call duration was 8 min. The cumulative time spent resolving outside calls during the study period was at least 41.25 hours. Sixty-three per cent of calls were from other acute hospitals in the region. Thirty-nine per cent of referrals were deemed incomplete with respect to either history, collateral history or examination. CONCLUSIONS: This is a necessary service in a system that is not adequately resourced to provide specialist led care in all hospitals. A greater emphasis on complete and accurate referrals, along with robust communication and documentation, could reduce the inherent risk associated with such consultations.

Germline mosaicism in a family with MBD5 haploinsufficiency.

Haploinsufficiency of the methyl-CpG-binding domain protein 5 (MBD5) gene causes a neurodevelopmental disorder that includes intellectual disability, developmental delay, speech impairment, seizures, sleep disturbances, and behavioral difficulties. Microdeletion of 2q23.1 is the most common cause of haploinsufficiency, although MBD5 haploinsufficiency may also cause this genetic disorder. We report a family harboring a heterozygous loss-of-function variant in MBD5 (NM_018328.5:c.728delC; p.Pro243Hisfs*26), which includes three affected siblings with varying phenotypic features. Both parents were phenotypically normal but deep coverage sequencing of the parents showed germline mosaicism in the mother.

Evaluation of Systemwide Improvement Programs to Optimize Time to Surgery for Patients With Hip Fractures: A Systematic Review.

Importance: Longer time to surgery (TTS) for hip fractures has been associated with higher rates of postoperative complications and mortality. Given that more than 300 000 adults are hospitalized for hip fractures in the United States each year, various improvement programs have been implemented to reduce TTS with variable results, attributed to contextual patient- and system-level factors. Objective: To catalog TTS improvement programs, identify their results, and categorize program strategies according to Expert Recommendations for Implementing Change (ERIC), highlighting components of successful improvement programs within their associated contexts and seeking to guide health care systems in implementing programs designed to reduce TTS. Evidence Review: A systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Three databases (MEDLINE/PubMed, EMBASE, and Cochrane Trials) were searched for studies published between 2000 and 2021 that reported on improvement programs for hip fracture TTS. Observational studies in high-income country settings, including patients with surgical, low-impact, nonpathological hip fractures aged 50 years or older, were considered for review. Improvement programs were assessed for their association with decreased TTS, and ERIC strategies were matched to improvement program components. Findings: Preliminary literature searches yielded 1683 articles, of which 69 articles were included for final analysis. Among the 69 improvement programs, 49 were associated with significantly decreased TTS, and 20 programs did not report significant decreases in TTS. Among 49 successful improvement programs, the 5 most common ERIC strategies were (1) assess for readiness and identify barriers and facilitators, (2) develop a formal implementation blueprint, (3) identify and prepare champions, (4) promote network weaving, and (5) develop resource-sharing agreements. Conclusions and Relevance: In this systematic review, certain components (eg, identifying barriers and facilitators to program implementation, developing a formal implementation blueprint, preparing intervention champions) are common among improvement programs that were associated with reducing TTS and may inform the approach of hospital systems developing similar programs. Other strategies had mixed results, suggesting local contextual factors (eg, operating room availability) may affect their success. To contextualize the success of a given improvement program across different clinical settings, subsequent investigation must elucidate the association between interventional success and facility-level factors influencing TTS, such as hospital census and type, teaching status, annual surgical volume, and other factors.

Asymptomatic idiopathic intracranial hypertension post female to male gender transition.

A 23- year-man post female to male (FTM) gender transition was found to have bilateral papilloedema at a routine optician visit. The patient was referred on for formal ophthalmological and neurological assessments. Optical coherence tomography (OCT) confirmed the presence of bilateral papilloedema. The patient was entirely asymptomatic and had no medical history. He took testosterone intramuscularly once per month. Neurological examination was otherwise normal. Investigations including routine blood panels, CT brain, MRI brain and cerebral MR venogram were all normal. Lumbar puncture yielded cerebrospinal fluid (CSF) normal in appearance but demonstrated raised intracranial pressure. In the absence of other causative aetiologies a diagnosis of idiopathic intracranial hypertension (IIH) was made. Treatment was commenced with acetazolamide and the patient was discharged with outpatient ophthalmological and neurological follow-up.

Vocal cord paralysis as a presenting sign of autosomal recessive spinocerebellar atrophy type 10.

Acquired vocal cord paralysis (VCP) is caused by dysfunction or injury of one or both recurrent laryngeal nerves. Here we report a 41-year-old man with spinocerebellar atrophy, autosomal recessive type 10 (SCAR10) due to an autosomal recessive mutation in the ANO10 gene, with VCP as the presenting symptom. He later developed ataxia and speech disturbance.

Change in urban and non-urban pattern of ED use during the COVID-19 pandemic in 28 Michigan hospitals: an observational study.

OBJECTIVE: To assess the trends in visits, overall and by age, to urban and non-urban emergency departments (EDs), and visits resulting in admission to hospital before and during the COVID-19 pandemic using a large regional database. SETTING: A large regional database of 28 EDs during the COVID-19 pandemic in Michigan, with an index case of 11 March 2020 and peak in the first week of April. PARTICIPANTS: ED visits during the first 5 months of the calendar year were included and compared with the previous year. Facilities where these participants were seen were classified as urban or non-urban, with comparisons of total visits, COVID-like cases, paediatric and trauma. OUTCOME MEASURES: Daily visits to EDs of patients presenting with COVID-like symptoms, trauma, age patterns and total cases, and stratified between urban and non-urban settings. RESULTS: There were 1 732 852 visits across the 2 years, 953 407 between study and comparison periods, and 457 130 visits defined as COVID-like (median age 44 years). Total ED visits decreased to 48% of the previous year, showing a delayed-inverse relationship with COVID-19. Trauma cases dropped but returned to the pre-COVID-19 rate by the end of May in Urban centres. Paediatric cases decreased to 20% of the previous year by the end of April. The oldest age groups showed the least change in ED visits in response to the pandemic. CONCLUSIONS: This large US Midwestern state study describes a dramatic decrease in ED visits after the onset of the COVID-19 pandemic in Michigan, including stratification by varying ages and trauma, demonstrating the tangible impact of the COVID-19 pandemic on urban and non-urban EDs.

Late-Onset Tay-Sachs Disease in an Irish Family.

BACKGROUND: Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive lysosomal storage disease caused by deficient ß-hexosaminidase A activity. LOTS is rare in the Ashkenazi Jews, but even rarer in the non-Jewish population. CASES: We report an Irish family expanding the LOTS phenotype (ataxia, diffuse muscle wasting, dystonia, chorea, belly dancer's dyskinesia, and neuropsychiatric features) associated with the known HEXA variant 1073 + 1G > A and a novel variant c.459 + 24G > C. CONCLUSIONS: LOTS should be considered in patients with similar symptoms and cerebellar atrophy on brain imaging.

A rapid method for analysis of non-equilibrated 90Sr/90Y in infant formula.

A rapid analytical method for quantifying 90Sr in infant formula prior to secular equilibrium is presented. The approach is dependent on the use of two separations of 90Sr from 90Y, with the first providing an 90Y ingrowth start point and the second providing an 90Y ingrowth end point. Data were obtained at activity concentrations of approximately 6 Bq/kg and 160 Bq/kg, the latter of which is representative of the US Food and Drug Administration (FDA) Derived Intervention Levels (DIL). Experiments were designed to collect data from ingrowth periods ranging from 16 h to 2 weeks. Activities obtained with a separation interval as low as 16 h ranged from 92.7 to 109.4% of the known value. When 90Y ingrowth was allowed to occur for 24 h or longer, the activities ranged from 93.2 to 106.2% of the known value and the precision of this group improved from 5.2 to 3.1%. The limit of quantification (LOQ) was 0.5 Bq/kg using 250 g sample portions.

'Should have gone to ': bilateral papilloedema with normal CSF pressure due to vestibular schwannoma.

A 24-year-old woman presented with bilateral blurring of her distance vision and 'dizzy spells'. She had no other neurological symptoms or medical history. She consulted an optometrist, and optical coherence tomography (OCT) was performed, which demonstrated papilloedema. She was referred to the local eye clinic for assessment and from there was referred for neurological assessment.Her initial investigations revealed no abnormalities, and brain imaging was reported to be normal. In the absence of an alternative diagnosis, idiopathic intracranial hypertension (IIH) was considered and a lumbar puncture was performed. This showed elevated protein but normal cerebrospinal fluid (CSF) pressure. MRI of the brain the next day revealed a large cerebellopontine lesion in keeping with vestibular schwannoma. She was referred to neurosurgery for operative management.This case highlights three interesting points: the aetiology of her papilloedema without raised intracranial pressure, the decision to perform a lumbar puncture in suspected IIH and community OCT as a clinical adjunct.

NADPH oxidase 4 is protective and not fibrogenic in intestinal inflammation.

Dysregulated redox signaling and oxidative injury are associated with inflammatory processes and fibrosis. H2O2 generation by NOX4 has been suggested as a key driver in the development of fibrosis and a small molecule drug is under evaluation in clinical trials for idiopathic pulmonary fibrosis and primary biliary cholangitis. Fibrosis is a common complication in Crohn's disease (CD) leading to stricture formation in 35-40% of patients, who require surgical interventions in the absence of therapeutic options. Here we assess NOX4 expression in CD patients with inflammatory or stricturing disease and examine whether loss of NOX4 is beneficial in acute and fibrotic intestinal disease. NOX4 was upregulated in inflamed mucosal tissue of CD and ulcerative colitis (UC) patients, in CD ileal strictures, and in mice with intestinal inflammation. Nox4 deficiency in mice promoted pathogen colonization and exacerbated tissue injury in acute bacterial and chemical colitis. In contrast, in two chronic injury models aberrant tissue remodeling and fibrosis-related gene expression did not differ substantially between Nox4-/- mice and wildtype mice, suggesting that Nox4 is dispensable in TGF-ß1-driven intestinal fibrogenesis. While animal models do not recapitulate all the hallmarks of CD fibrosis, the tissue-protective role of Nox4 warrants a cautious approach to pharmacological inhibitors.

Patient and service-level factors affecting length of inpatient stay in an acute mental health service: a retrospective case cohort study.

BACKGROUND: The NHS Mental Health Implementation Plan aims to reduce length of inpatient psychiatric stays to a maximum of 32 days, yet provides little guidance on how to achieve this. Previous studies have attempted to analyse factors influencing length of stay in mental health units, focussing mostly on patient factors. These models fail to sufficiently explain the variation in duration of inpatient stay. We assess how the type of service delivered by a trust, in addition to patient factors, influences length of stay. METHODS: We conducted a retrospective case cohort study in a large inner-city NHS mental health trust for all admissions in a 1 month period. Data was gathered from electronic notes of 105 patients. Descriptive univariate and bivariate analyses were conducted on the data, with multiple regression analysis conducted on statistically significant data. RESULTS: Short-stay assessment ward admission significantly reduced length of stay. Patients under outpatients or under care co-ordination, admitted through Mental Health Act assessment and formally detained all had longer length of stay. Out of area admissions, locum Consultant care, changing Responsible Clinician and ward transfers all led to longer length of stay. Factors indicating more severe illness such as increased observation level and polypharmacy, as well as diagnoses of psychosis or bipolar disorder were associated with longer duration of stay. Discharges requiring referral to accommodation or rehabilitation led to longer stays. The most significant factors that influenced length of stay were higher observation levels, diagnosis of psychotic illness or bipolar, and discharge to rehabilitation placement. The final model, taking into account all these factors, was able to account for 59.6% of the variability in length of stay. CONCLUSIONS: The study backs up existing literature which shows patient-factors have an influence on length of stay. The study also demonstrates that service-level factors have an impact on the duration of stay. This data may be used to inform further studies which may aid provision of inpatient and community services in the future.

Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy.

Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.

A comparison of genomic diagnostics in adults and children with epilepsy and comorbid intellectual disability.

Next generation sequencing provides an important opportunity for improved diagnosis in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the paediatric arena, while the utility of such testing is less well understood in adults with epilepsy. We conducted whole exome sequencing (WES) and copy number variant analyses in an Irish cohort of 101 people with epilepsy and co-morbid intellectual disability to compare the diagnostic yield of genomic testing between adult and paediatric patients. Variant interpretation followed American College of Medical Genetics and Genomics (ACMG) guidelines. We demonstrate that WES, in combination with array-comparative genomic hybridisation, provides a diagnostic rate of 27% in unrelated adult epilepsy patients and 42% in unrelated paediatric patients. We observe a 2.7% rate of ACMG-defined incidental findings. Our findings indicate that WES has similar utility in both adult and paediatric cohorts and is appropriate for diagnostic testing in both epilepsy patient groups.

The future of genomics in Ireland - focus on genomics for health.

Genomics is revolutionizing biomedical research, medicine and healthcare globally in academic, public and industry sectors alike. Concrete examples around the world show that huge benefits for patients, society and economy can be accrued through effective and responsible genomic research and clinical applications. Unfortunately, Ireland has fallen behind and needs to act now in order to catch up. Here, we identify key issues that have resulted in Ireland lagging behind, describe how genomics can benefit Ireland and its people and outline the measures needed to make genomics work for Ireland and Irish patients. There is now an urgent need for a national genomics strategy that enables an effective, collaborative, responsible, well-regulated, and patient centred environment where genome research and clinical genomics can thrive.  We present eight recommendations that could be the pillars of a national genomics health strategy.

Cycle ergometer training enhances plasma interleukin-10 in multiple sclerosis.

The objective was to determine plasma levels of pro- (IL-12p70/IL-6) and anti-inflammatory (IL-10) cytokines before and after cycle ergometer training in healthy control (HC) and people with multiple sclerosis (pwMS), and to correlate plasma cytokines with physical/mental health. Study participants cycled for 30 min at 65-75% age-predicted maximal heart rate, twice a week for 8 weeks during supervised sessions. We determined that plasma IL-10 expression was lower in pwMS, compared to HCs, and that exercise augmented IL-10 in pwMS to baseline levels in HCs. Furthermore, plasma isolated from pwMS displayed enhanced expression of the pro-inflammatory cytokines IL-12p70/IL-6. Plasma cytokine signatures correlated with physical/mental health. Overall, this study highlights the potential of a short-term exercise programme to regulate circulating cytokine profiles with relevance to pwMS.

Correction to: Cycle ergometer training enhances plasma interleukin-10 in multiple sclerosis.

Following publication the authors informed the Journal that the published version of this article contained a mistake. All occurrences of pg/µl found in the original article should be changed to pg/L. The original article has been corrected. The correction has no impact on the conclusions drawn in the manuscript.