'Small volume-big problem': culturing Yarrowia lipolytica in high-throughput micro-formats.

With the current progress in the 'design' and 'build' stages of the 'design-build-test-learn' cycle, many synthetic biology projects become 'test-limited'. Advances in the parallelization of microbes cultivations are of great aid, however, for many species down-scaling leaves a metabolic footprint. Yarrowia lipolytica is one such demanding yeast species, for which scaling-down inevitably leads to perturbations in phenotype development. Strictly aerobic metabolism, propensity for filamentation and adhesion to hydrophobic surfaces, spontaneous flocculation, and high acidification of media are just several characteristics that make the transfer of the micro-scale protocols developed for the other microbial species very challenging in this case. It is well recognized that without additional 'personalized' optimization, either MTP-based or single-cell-based protocols are useless for accurate studies of Y. lipolytica phenotypes. This review summarizes the progress in the scaling-down and parallelization of Y. lipolytica cultures, highlighting the challenges that occur most frequently and strategies for their overcoming. The problem of Y. lipolytica cultures down-scaling is illustrated by calculating the costs of micro-cultivations, and determining the unintentionally introduced, thus uncontrolled, variables. The key research into culturing Y. lipolytica in various MTP formats and micro- and pico-bioreactors is discussed. Own recently developed and carefully pre-optimized high-throughput cultivation protocol is presented, alongside the details from the optimization stage. We hope that this work will serve as a practical guide for those working with Y. lipolytica high-throughput screens.

Updated protocol for genetic testing, screening and clinical management of individuals at risk of NF2-related schwannomatosis.

Genetic testing and management of individuals at risk for NF2-related schwannomatosis is complicated by the high rate of mosaicism resulting in a milder, later onset, more asymmetrical disease and the phenotypic overlap with the related schwannomatosis conditions. This updated protocol has been devised for the English NF2-related schwannomatosis service. It provides those affected with mosaic NF2-related schwannomatosis estimated risks of having an affected child; and management guidelines both for individuals at risk of NF2-related schwannomatosis, or with potential disease, due to having features that fall short of consensus diagnostic criteria. Risks of mosaicism and inferred transmission risks were derived from genetic testing of over 1000 individuals through the Manchester NF2 genetic testing service. This updated protocol, reflects the lower transmission risks now inferred in mosaic NF2-related schwannomatosis, informed by the greater sensitivity of Next Generation Sequencing in detecting low levels of mosaicism in blood, along with improved ability to analyse tumour DNA. Screening for features of NF2-related schwannomatosis is proposed until the risk of having the condition falls below a pragmatic threshold of 1%. Using these revised transmission figures, this threshold can now be reached at a younger age in many of those at risk, with earlier reassurance and discharge.

Evaluating the Routine Use of Head Computed Tomography Angiography in Blunt Cerebrovascular Trauma.

BACKGROUND: The aim of this study was to evaluate a protocol change that mandated routine incorporation of head computed tomography angiography (CTA) for the work-up of suspected blunt cerebrovascular injury (BCVI) at an academic Level I trauma center. METHODS: The BCVI screening guidelines at our institution changed in 2018 to include the addition of a head CTA for all patients receiving a neck CTA as part of our BCVI screening guidelines. We performed a retrospective chart review of patients between 2018 and 2019 who were 18 years or older and met screening criteria for BCVI based on our institutional guidelines. The head CTAs of this cohort were assessed for findings that could potentially alter the course of the patients' treatment. RESULTS: A total of 319 patients fit this criterion and had a head CTA as part of their trauma workup. Findings that could potentially alter a patient's clinical course were identified in 6.6% (n = 21) of the head CTA's. These included decreased arterial perfusion (n = 9), active bleeds (n = 6), vessel occlusions (n = 1), aneurysms (n = 1), and vasospasms (n = 2). Of these 21 patients, 8 had clinically significant findings that affected their course of management (2.5% of total sample). They also had a higher mortality rate and ISS compared to the rest of the cohort. CONCLUSIONS: In patients with clinically suspected BCVI, the addition of head CTA to the existing BCVI screening guideline identified clinically significant vascular abnormalities that affected management in 2.5% of cases.

Quality improvement project to increase screening and referral for biologic therapy for patients with uncontrolled asthma.

BACKGROUND: Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. METHODS: A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. RESULTS: Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. CONCLUSIONS: The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.

Assessment of hearing screening programmes across 47 countries or regions I: provision of newborn hearing screening.

OBJECTIVES: Newborn hearing screening (NHS) varies regarding number and type of tests, location, age, professionals and funding. We compared the provision of existing screening programmes. DESIGN: A questionnaire containing nine domains: demography, administration, existing screening, coverage, tests, diagnosis, treatment, cost and adverse effects, was presented to hearing screening experts. Responses were verified. Clusters were identified based on number of screening steps and use of OAE or aABR, either for all infants or for well and high-risk infants (dual-protocol). STUDY SAMPLE: Fifty-two experts completed the questionnaire sufficiently: 40 European countries, Russia, Malawi, Rwanda, India and China. RESULTS: It took considerable effort to find experts for all countries with sufficient time and knowledge. Data essential for evaluation are often not collected. Infants are first screened in maternity wards in most countries. Human development index and health expenditure were high among countries with dual protocols, three screening steps, including aABR, and low among countries without NHS and countries using OAE for all infants. Nationwide implementation of NHS took 6 years, on average. CONCLUSION: The extent and complexity of NHS programmes are primarily related to health expenditure and HDI. Data collection should be improved to facilitate comparison of NHS programmes across borders.

Assessment of hearing screening programmes across 47 countries or regions III: provision of childhood hearing screening after the newborn period.

OBJECTIVE: To inventory provision and features of childhood hearing screening after the newborn period (CHS), primarily in Europe. DESIGN: From each participating country or region, experts provided information through an extensive questionnaire: implementation year, age at screening, test method, pass criteria, screening location, screener profession, and quality indicators: coverage, referral, follow-up and detection rates, supplemented by literature sources. STUDY SAMPLE: Forty-two European countries or regions, plus Russia, Malawi, Rwanda, India, and China. RESULTS: CHS was performed universally with pure-tone audiometry screening (PTS) in 17 countries or regions, whereas non-universal CHS was performed in eight with PTS or whisper tests. All participating countries with universal PTS had newborn hearing screening. Coverage rate was provided from three countries, detection rate from one, and referral and follow-up rate from two. In four countries, universal PTS was performed at two ages. Earliest universal PTS was performed in a (pre)school setting by nurses (n = 9, median age: 5 years, range: 3-7), in a healthcare setting by doctors and nurses (n = 7, median age: 4.5 years, range: 4-7), or in both (n = 1). CONCLUSIONS: Within universal CHS, PTS was mostly performed at 4-6 years by nurses. Insufficient collection of data and monitoring with quality indicators impedes evaluation of screening.

Noncontact Body Temperature Measurement: Uncertainty Evaluation and Screening Decision Rule to Prevent the Spread of COVID-19.

The need to measure body temperature contactless and quickly during the COVID-19 pandemic emergency has led to the widespread use of infrared thermometers, thermal imaging cameras and thermal scanners as an alternative to the traditional contact clinical thermometers. However, limits and issues of noncontact temperature measurement devices are not well known and technical-scientific literature itself sometimes provides conflicting reference values on the body and skin temperature of healthy subjects. To limit the risk of contagion, national authorities have set the obligation to measure body temperature of workers at the entrance to the workplace. In this paper, the authors analyze noncontact body temperature measurement issues from both clinical and metrological points of view with the aim to (i) improve body temperature measurements accuracy; (ii) estimate the uncertainty of body temperature measurement on the field; (iii) propose a screening decision rule for the prevention of the spread of COVID-19. The approach adopted in this paper takes into account both the traditional instrumental uncertainty sources and clinical-medical ones related to the subjectivity of the measurand. A proper screening protocol for body temperature measurement considering the role of uncertainty is essential to correctly choose the threshold temperature value and measurement method to access critical places during COVID-19 pandemic emergency.

Searching for the Best Transthyretin Aggregation Protocol to Study Amyloid Fibril Disruption.

Several degenerative amyloid diseases, with no fully effective treatment, affect millions of people worldwide. These pathologies-amyloidoses-are known to be associated with the formation of ordered protein aggregates and highly stable and insoluble amyloid fibrils, which are deposited in multiple tissues and organs. The disruption of preformed amyloid aggregates and fibrils is one possible therapeutic strategy against amyloidosis; however, only a few compounds have been identified as possible fibril disruptors in vivo to date. To properly identify chemical compounds as potential fibril disruptors, a reliable, fast, and economic screening protocol must be developed. For this purpose, three amyloid fibril formation protocols using transthyretin (TTR), a plasma protein involved in several amyloidoses, were studied using thioflavin-T fluorescence assays, circular dichroism (CD), turbidity, dynamic light scattering (DLS), and transmission electron microscopy (TEM), in order to characterize and select the most appropriate fibril formation protocol. Saturation transfer difference nuclear magnetic resonance spectroscopy (STD NMR) was successfully used to study the interaction of doxycycline, a known amyloid fibril disruptor, with preformed wild-type TTR (TTRwt) aggregates and fibrils. DLS and TEM were also used to characterize the effect of doxycycline on TTRwt amyloid species disaggregation. A comparison of the TTR amyloid morphology formed in different experimental conditions is also presented.

Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening.

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.

A genome-wide RNAi screening method to discover novel genes involved in virus infection.

Systematic and comprehensive analysis of host cell proteins involved in virus infection has been difficult in large part due to the lack of robust unbiased methods for their identification. Recent technological breakthroughs allowing development of cell-based genetic screens have greatly facilitated our understanding of virus-host interactions. These include instrumentation for processing in microtiter plates (e.g., 384 well), coupled with sensitive readers and off-the-shelf analysis and informatics pipelines. Because viruses are a significant threat to human health, a better understanding of the cellular factors that impact infection would pave the way for the development of new therapeutics. Here we describe the development and implementation of a genome-wide siRNA screen against a virus using human cells.

A proposal for using contralateral teeth to provide well-balanced experimental groups for endodontic studies.

AIM: To develop a suitable protocol for screening extracted teeth so as to create anatomically well-balanced experimental groups for endodontic studies. METHODOLOGY: Sixty pairs (120 teeth) of contralateral premolars (CLPs) were collected. The evaluation of samples for anatomical features was performed in the following ways. First, the 120 teeth were divided into right and left sides (N = 60, each side), and the teeth of each side were screened individually according to regular inclusion criteria (parameters included mature apical foramen, canal type, canal curvature and tooth length). The similarity of the specimens was then evaluated. The second screening process evaluated the 60 pairs of CLPs using the same criteria. Finally, CBCT was used to establish a strict screening protocol to create well-balanced groups of CLPs. RESULTS: In the first screening process, 80% (24/30) of the left and 61% (19/31) of the right side were selected out of teeth with mature foramina; but the included teeth had asymmetrical canal curvatures. In the second screening process, 28 pairs were selected after the exclusion of those with an immature foramen in one pair. Seventeen pairs in which the tooth length and canal curvature were symmetrical were selected from the 28 CLPs. In the third screening, only 21% (6/28) of CLPs passed the rigorous screening procedure and were identical for creating balanced experimental groups. CONCLUSIONS: Relatively, few pairs of contralateral teeth had anatomical symmetry. For endodontic studies, a strict and detailed scientific screening protocol is necessary to achieve well-balanced experimental groups.

Recovering Misidentified Samples Through Genetic Discordance Clustering.

The many logistical and technical challenges associated with sample and data handling in largescale genotyping studies can increase the risk of sample misidentification, which may compromise subsequent analyses. However, the standard quality assurance methods typical for large genotyping arrays can often be further utilized to identify and recover problematic samples. This article emphasizes the importance of identifying and correcting underlying sample misidentification rather than simply excluding known discrepancies, which may potentially include undetected issues. Lastly, we provide a screening protocol to complement standard quality assessments as a guideline for identifying mismatched samples and a tool for assessing the most common causes of sample misidentification. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.

The molecular detection of carbapenem markers with a two-levels amplification screening protocol: epidemiological and resistome insights.

Objectives: Carbapenem-resistance is a challenging healthcare concern and require specific stewardship programs. Monitoring workflows include the identification from surveillance samples, such as rectal swabs. Although culture assays represent the gold standard, data report a significant effectiveness in detecting carbapenemases genes directly from rectal swabs. The aim of this study was to evaluate the REALQUALITY Carba-Screen kit (AB ANALITICA, Padova, Italy) in detecting carbapenemases genes directly from rectal swabs, also comparing its effectiveness to culture assays results. A next-generation sequencing (NGS) was performed to investigate the positive samples about resistance markers and sequence type (ST). Methods: A number of 136 rectal swabs were collected from the University Hospital Policlinico of Catania critical wards. The samples simultaneously underwent culture and molecular assays (REALQUALITY Carba-Screen kit). The molecular method included two-steps. The first step (1 h and 6 min) rapidly excluded negative samples, while the second one (1 h and 6 min) included only positive samples for a resistance confirmation. All the positive culture samples underwent NGS analysis. Results: Statistical evaluations demonstrated high sensitivity (100%) and detection rates (92.6%) for the REALQUALITY Carba-Screen kit, which mostly correlated to the standard workflow. All the culture positive results matched the positive molecular results, which were mainly confirmed by the NGS resistome analysis. The identified ST appeared to be diversified and different from the clinically significative strains of the same setting, furnishing interesting epidemiological evidence. Conclusion: The molecular detection allowed a coordinate approach in a high-prevalence multi-drug-resistance area. The rapid identification with a multi-step procedure accelerated the infection control procedures, while the preliminary negative results reduced the overtreatment episodes. The molecular method efficacy was confirmed through the NGS. In conclusion, the molecular screening could initially lead to a more conservative approach, which may be reevaluated after a culture result about the microorganisms' identification and susceptibility profile.

Autosomal dominant hypercholesterolemia: needs for early diagnosis and cascade screening in the tunisian population.

Autosomal dominant hypercholesterolemia (ADH) is characterized by an isolated elevation of plasmatic low-density lipoprotein (LDL), which predisposes to premature coronary artery disease (CAD) and early death. ADH is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). Early diagnosis and initiation of treatment can modify the disease progression and its outcomes. Therefore, cascade screening protocol with a combination of plasmatic lipid measurements and DNA testing is used to identify relatives of index cases with a clinical diagnosis of ADH. In Tunisia, an attenuated phenotypic expression of ADH was previously reported, indicating that the establishment of a special screening protocol is necessary for this population.

Procedure, Screening, and Cost of Fecal Microbiota Transplantation.

Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.

Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy).

Objectives: We validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as "case study" for this purpose. Methods: From July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan. Results: On a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations. Conclusion: A first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer. Protocol registration code: PLEURO-SCREENING-V1.0_15 Feb, 17.

Reconstruction of SARS-CoV-2 outbreaks in a primary school using epidemiological and genomic data.

Mathematical modelling studies have shown that repetitive screening can be used to mitigate SARS-CoV-2 transmission in primary schools while keeping schools open. However, not much is known about how transmission progresses within schools and whether there is a risk of importation to households. During the academic year 2020-2021, a prospective surveillance study using repetitive screening was conducted in a primary school and associated households in Liège (Belgium). SARS-CoV-2 screening was performed via throat washing either once or twice a week. We used genomic and epidemiological data to reconstruct the observed school outbreaks using two different models. The outbreaker2 model combines information on the generation time and contact patterns with a model of sequence evolution. For comparison we also used SCOTTI, a phylogenetic model based on the structured coalescent. In addition, we performed a simulation study to investigate how the accuracy of estimated positivity rates in a school depends on the proportion of a school that is sampled in a repetitive screening strategy. We found no difference in SARS-CoV-2 positivity between children and adults and children were not more often asymptomatic compared to adults. Both models for outbreak reconstruction revealed that transmission occurred mainly within the school environment. Uncertainty in outbreak reconstruction was lowest when including genomic as well as epidemiological data. We found that observed weekly positivity rates are a good approximation to the true weekly positivity rate, especially in children, even when only 25% of the school population is sampled. These results indicate that, in addition to reducing infections as shown in modelling studies, repetitive screening in school settings can lead to a better understanding of the extent of transmission in schools during a pandemic and importation risk at the community level.

Case report: Tuberculosis recall on bone graft patient.

Background: Bone grafting is commonly used in spine surgery to supplement or replace the need for autografts. This is harvested, prepared, and utilized predominantly for osteoconductive properties. Anterior cervical discectomy and fusion, a procedure to decompress and fuse the spine which treats herniated discs and compressed nerves, commonly uses Polyetheretherketone (PEEK) interbody filled with allograft bone matrices to reconstruct the disc space after a discectomy is performed. Case Description: The presented case is one of a 57-year-old male patient who underwent an uneventful cervical 5-6 and cervical 6-7 discectomy and fusion using a PEEK interbody and bone allograft. The allograft had been prepared using cancellous bone particles with preserved living cells and demineralized cortical bone fibers to facilitate bone repair and healing, which is a common technique. The allograft was aseptically processed to preserve native factors that can support bone repair and prevent contamination and cross-contamination of the product. Additionally, the product was sterilized using gamma irradiation to further prevent contamination. Outcome: Unfortunately, with the presented case, the State's Department of Health and The Center for Diseases Control and Prevention identified that the graft was from a source contaminated with tuberculosis. The patient being reported went on to develop disseminated tuberculosis, including lung abscesses and osteomyelitis. Conclusions: The current case highlights that there was contamination of the donor bone sources. Tuberculosis was not screened in the tissue donor even though he had risk factors, symptoms, and signs consistent with tuberculosis. Although there are methods to screen potential organ donors for tuberculosis, there is currently no approved standard laboratory tuberculosis screening tool for bone grafts. Thus, this emphasizes the importance of proper screening among individual institutions for even the most uncommon diseases in all donated bone grafts.

Evaluation of Protocol for Assessing the Reaction of Rice and Wheat Germplasm to Infection by Meloidogyne graminicola.

Root-knot nematode (Meloidogyne graminicola), an important and widespread pathogen, causes high yield losses in rice with limited information on wheat and on efficient management. Absence of uniform screening protocols is contributing to slow progress of host resistance development. To develop an efficient screening protocol, several greenhouse studies were conducted, and effects of incubation period, inoculum level, inoculation method, seedling age, and their interactions on root-galling severity (RGS) ratings and reproductive factor (RF) values of M. graminicola were determined. At 2 eggs/cm(3) soil, significantly lower RGS but higher RF values were observed at 60 days than at 45 days of incubation. Meloidogyne graminicola reproduced six times more on rice than on wheat where the RGS index in both crops increased steadily with increasing inoculum levels, but RF increased at lower levels and decreased beyond a maximum at medium inoculum levels. Inoculum level, container size, seedling age, inoculation method, and their interactions impacted nematode infection and reproduction. The protocol was verified on eleven rice germplasm lines and seven wheat cultivars using the resistance index (RI) calculated from RGS and RF, to screen rice and wheat germplasm.

Delayed symptomatic hyponatremia in transsphenoidal surgery: Systematic review and meta-analysis of its incidence and prevention with water restriction.

BACKGROUND: Delayed symptomatic hyponatremia (DSH) is an unpredictable postoperative complication after transsphenoidal pituitary surgery. Universal postoperative sodium screening and water restriction are two strategies to detect or prevent the development of DSH. We performed a meta-analysis of studies characterizing the rate of DSH using sodium screening and water restriction protocols. METHODS: Literature search was done using MEDLINE/PUBMED, EMBASE, and Cochrane databases. Inclusion criteria are (1) development of DSH after endoscopic or microscopic transsphenoidal, sellar surgery, and (2) reporting of a standardized postoperative sodium screening protocol for monitoring or prevention of DSH. RESULTS: A total of 23 publications fulfilled the inclusion criteria resulted in a total of 5870 patients. Two meta-analyses were conducted. Of the 19 studies (N = 4488 patients) examining rate of DSH after sodium screening, DSH rates ranged from 0% to 19.7%. In the first meta-analysis, using a random-effect estimate of the combined proportions, the overall rate of DSH was 5.60% (4.0%-7.1%, I2 = 96.54%, T2 = 0.0007). In the second meta-analysis, a fixed-effect model of four studies consisted of 1382 patients. Eight hundred fifty-two patients were included prior to and 530 were included after water restriction protocol. Meta-analysis showed an odds ratio (OR) of 5.02 (95% CI: 2.16-11.65) favoring water restriction. CONCLUSION: This meta-analysis summarized rates of DSH with sodium screening protocol to be 5.60% (4.0%-7.1%) and showed a decreased risk of DSH after implementation of a water restriction protocol. The results are limited due to few studies examining fluid restriction (N = 4) and heterogeneity in water restriction protocols. No adverse events were seen with fluid restriction protocol. Prospective and multicenter studies should be conducted to further investigate the utility of water restriction following transsphenoidal pituitary surgery.