CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

PURPOSE: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system. METHODS: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences. RESULTS: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models. CONCLUSION: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients.

Perfusion index as a predictor of working pediatric caudal block under general anesthesia- A prospective observational study.

Background and Aims: Advances in pulse oximeter technology have enabled us to measure parameters such as perfusion index (PI). We aimed to ascertain the utility of PI in the lower limb for evaluating the onset and adequacy of the pediatric caudal block under general anesthesia. The primary objective was to monitor PI trends after caudal block. The secondary objective was to compare the role of PI, heart rate (HR), and mean arterial pressure (MAP) in detecting onset and adequacy of caudal block and to ascertain whether PI was an earlier indicator in detecting adequate block. Material and Methods: Twenty-five children between 1 and 6 years, who underwent general anesthesia (GA) with caudal block were included. Baseline PI, HR, and MAP were recorded prior to and post caudal block at 5, 10, 15, 20 min and on skin incision. The onset of adequate block was defined as 100% increase of PI from baseline, 15% decrease of MAP or HR from baseline. T-test was used to compare trends of PI with baseline and the number of patients who met or failed these criteria for each of these three parameters at various time intervals wasnoted. Results: PI increased at all time intervals in 23 of 25 patients with working caudal block (P < 0.0001). By 10 min all those with a working caudal showed a 100% increase in PI. In contrast, 15% decrease in HR was not attained until 15 min where only 8 out of 23 achieved the above criteria, reaching a maximum of 20 patients at the time of incision; a 15% decrease in MAP was observed only in one patient at 5 min, reaching a maximum of eight patients at the time of incision. Conclusion: PI is an earlier and more sensitive indicator of the onset of the caudal block under general anesthesia (GA) than HR and MAP.

gdnf affects early diencephalic dopaminergic neuron development through regulation of differentiation-associated transcription factors in zebrafish.

Glial cell line-derived neurotrophic factor (GDNF) has been reported to enhance dopaminergic neuron survival and differentiation in vitro and in vivo, although those results are still being debated. Glial cell line-derived neurotrophic factor (gdnf) is highly conserved in zebrafish and plays a role in enteric nervous system function. However, little is known about gdnf function in the teleost brain. Here, we employed clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 to impede gdnf function in the maintenance of dopaminergic neuron development. Genotyping of gdnf crispants revealed successful deletions of the coding region with various mutant band sizes and down-regulation of gdnf transcripts at 1, 3 and 7 day(s) post fertilization. Notably, ~20% reduction in ventral diencephalic dopaminergic neuron numbers in clusters 8 and 13 was observed in the gdnf-deficient crispants. In addition, gdnf depletion caused a modest reduction in dopaminergic neurogenesis as determined by 5-ethynyl-2'-deoxyuridine pulse chase assay. These deleterious effects could be partly attributed to deregulation of dopaminergic neuron fate specification-related transcription factors (otp,lmx1b,shha,and ngn1) in both crispants and established homozygous mutants with whole mount in-situ hybridization (WISH) on gdnf mutants showing reduced otpb and lmx1b.1 expression in the ventral diencephalon. Interestingly, locomotor function of crispants was only impacted at 7 dpf, but not earlier. Lastly, as expected, gdnf deficiency heightened crispants vulnerability to 1-methyl-4-phenylpyridinium toxic insult. Our results suggest conservation of teleost gdnf brain function with mammals and revealed the interactions between gdnf and transcription factors in dopaminergic neuron differentiation.

A retrospective multi-center experience of renal transplants from India during COVID-19 pandemic.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. METHODS: This was a retrospective, observational, multi-center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. RESULTS: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002-1.077). CONCLUSIONS: Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio.

Functional analysis of iron-sulfur cluster biogenesis (SUF pathway) from Plasmodium vivax clinical isolates.

Iron-sulfur (Fe-S) clusters are critical metallo-cofactors required for cell function. Assembly of these cofactors is a carefully controlled process in cells to avoid toxicity from free iron and sulfide. In Plasmodium, two pathways for these Fe-S cluster biogenesis have been reported; ISC pathway in the mitochondria and SUF pathway functional in the apicoplast. Amongst these, SUF pathway is reported essential for the apicoplast maintenance and parasite survival. Many of its components have been studied from P. falciparum and P. berghei in recent years, still few queries remain to be addressed; one of them being the assembly and transfer of Fe-S clusters. In this study, using P. vivax clinical isolates, we have shown the in vitro interaction of SUF pathway proteins SufS and SufE responsible for sulfur mobilization in the apicoplast. The sulfur mobilized by the SufSE complex assembles on the scaffold protein PvSufA along with iron provided by the external source. Here, we demonstrate in vitro transfer of these labile Fe-S clusters from the scaffold protein on to an apo-protein, PvIspG (a protein involved in penultimate step of Isoprenoids biosynthesis pathway) in order to provide an insight into the interaction of different components for the biosynthesis and transfer of Fe-S clusters. Our analysis indicate that inspite of the presence of variations in pathway proteins, the overall pathway remains well conserved in the clinical isolates when compared to that reported in lab strains.

Temperature-sensitive liposome-mediated delivery of thrombolytic agents.

BACKGROUND: Clinical efficacy of thrombolytic drugs is limited by lack of specific delivery and requires large therapeutic doses which increase toxicity. Encapsulating these drugs in temperature-sensitive liposomes and applying hyperthermia to deliver thrombolytic agents locally to thrombus might theoretically favourably alter the therapeutic window. The objectives of this study were to formulate liposomes encapsulating thrombolytics and assess thrombolytic activity following hyperthermia. METHODS: Three liposome formulations were investigated: temperature-sensitive liposome (TSL, DPPC:DSPE-PEG2000 (mol% 95:5)), low temperature-sensitive liposome (LTSL, DPPC:MSPC:DSPE-PEG2000 (mol% 85.3:9.7:5)), and traditional temperature-sensitive liposome (TTSL, DPPC:HSPC:Chol:DSPE-PEG2000 (mol% 55:25:15:5)). To characterise temperature-dependent release of high molecular weight cargo from each formulation, fluorescein-conjugated dextrans (70 kDa) were loaded and release was quantified via spectrophotometry. Staphylokinase (SAK), urokinase, and tissue-type plasminogen activator were also loaded individually into each liposome formulation. Leakage at 37 °C and release at 38-44 °C were quantified via chromogenic enzymatic activity assay. Clot lysis was evaluated by measuring mass of blood clots before and after thrombolytic liposome treatment. RESULTS: The LTSL formulation had optimal release characteristics with maximum release at 41.3 °C. Release of dextrans from LTSLs was observed to be 11.5 ± 1.5%, 79.7 ± 1.6%, and 93.6 ± 3.7% after 15 min in plasma at 37°, 39°, and 41.3 °C, respectively. The SAK LTSL had the highest release/leakage ratio and demonstrated greater clot lysis. CONCLUSIONS: The SAK LTSL achieves significant clot lysis in vitro. When combined with local hyperthermia, the SAK LTSL potentially produces sufficient thrombolysis while minimising systemic side effects.

Natural antisense transcripts in Plasmodium falciparum isolates from patients with complicated malaria.

Mechanisms regulating gene expression in malaria parasites are not well understood. Little is known about how the parasite regulates its gene expression during transition from one developmental stage to another and in response to various environmental conditions. Parasites in a diseased host face environments which differ from the static, well adapted in vitro conditions. Parasites thus need to adapt quickly and effectively to these conditions by establishing transcriptional states which are best suited for better survival. With the discovery of natural antisense transcripts (NATs) in this parasite and considering the various proposed mechanisms by which NATs might regulate gene expression, it has been speculated that these might be playing a critical role in gene regulation. We report here the diversity of NATs in this parasite, using isolates taken directly from patients with differing clinical symptoms caused by malaria infection. Using a custom designed strand specific whole genome microarray, a total of 797 NATs targeted against annotated loci have been detected. Out of these, 545 NATs are unique to this study. The majority of NATs were positively correlated with the expression pattern of the sense transcript. However, 96 genes showed a change in sense/antisense ratio on comparison between uncomplicated and complicated disease conditions. The antisense transcripts map to a broad range of biochemical/metabolic pathways, especially pathways pertaining to the central carbon metabolism and stress related pathways. Our data strongly suggests that a large group of NATs detected here are unannotated transcription units antisense to annotated gene models. The results reveal a previously unknown set of NATs that prevails in this parasite, their differential regulation in disease conditions and mapping to functionally well annotated genes. The results detailed here call for studies to deduce the possible mechanism of action of NATs, which would further help in understanding the in vivo pathological adaptations of these parasites.

Steinman pin technique for the removal of well-fixed femoral stems.

Femoral stems with the capacity for exuberant bony in-growth, such as hydroxyapatite- or porous-coated stems, pose a challenge in the revision setting if extraction is required. The goal of minimal bone loss is crucial. We present an adjunct technique for the removal of well-fixed femoral stems with the use of Steinman pins.

Spiking CMOS-NVM mixed-signal neuromorphic ConvNet with circuit- and training-optimized temporal subsampling.

We increasingly rely on deep learning algorithms to process colossal amount of unstructured visual data. Commonly, these deep learning algorithms are deployed as software models on digital hardware, predominantly in data centers. Intrinsic high energy consumption of Cloud-based deployment of deep neural networks (DNNs) inspired researchers to look for alternatives, resulting in a high interest in Spiking Neural Networks (SNNs) and dedicated mixed-signal neuromorphic hardware. As a result, there is an emerging challenge to transfer DNN architecture functionality to energy-efficient spiking non-volatile memory (NVM)-based hardware with minimal loss in the accuracy of visual data processing. Convolutional Neural Network (CNN) is the staple choice of DNN for visual data processing. However, the lack of analog-friendly spiking implementations and alternatives for some core CNN functions, such as MaxPool, hinders the conversion of CNNs into the spike domain, thus hampering neuromorphic hardware development. To address this gap, in this work, we propose MaxPool with temporal multiplexing for Spiking CNNs (SCNNs), which is amenable for implementation in mixed-signal circuits. In this work, we leverage the temporal dynamics of internal membrane potential of Integrate & Fire neurons to enable MaxPool decision-making in the spiking domain. The proposed MaxPool models are implemented and tested within the SCNN architecture using a modified version of the aihwkit framework, a PyTorch-based toolkit for modeling and simulating hardware-based neural networks. The proposed spiking MaxPool scheme can decide even before the complete spatiotemporal input is applied, thus selectively trading off latency with accuracy. It is observed that by allocating just 10% of the spatiotemporal input window for a pooling decision, the proposed spiking MaxPool achieves up to 61.74% accuracy with a 2-bit weight resolution in the CIFAR10 dataset classification task after training with back propagation, with only about 1% performance drop compared to 62.78% accuracy of the 100% spatiotemporal window case with the 2-bit weight resolution to reflect foundry-integrated ReRAM limitations. In addition, we propose the realization of one of the proposed spiking MaxPool techniques in an NVM crossbar array along with periphery circuits designed in a 130nm CMOS technology. The energy-efficiency estimation results show competitive performance compared to recent neuromorphic chip designs.

A Case Report of Occult Weak 'A' Subgroup: An Important Message for Renal Transplant Physicians.

Accurate ABO grouping is the cornerstone of a successful ABO-compatible organ transplant. While conventional methods identify blood groups accurately in most cases, rare and weak blood groups could occasionally be misread/missed. Weak A subgroups such as A3, Ax, Aend, Am, Ay, and Ael are often mistyped as group O. We present one interesting case of 'weak A' subgroup in a renal transplant donor, who was wrongly typed as 'O' Rh D positive by conventional grouping techniques. It was a near miss as the donor was almost selected for transplant for the patient with blood group B positive.

Continuous Erector Spinae Plane Block in Paediatric VATS: A Case Series.

Decortication and stripping of infected pleura by video-assisted thoracoscopic surgery or thoracotomy is the treatment of choice in cases of empyema. The stripping is associated with intense post-operative pain. Erector spinae block is an excellent and safe alternative to thoracic epidural block. The experience in paediatric erector spinae plane block is very limited. We present our experience of continuous erector spinae block and one single-shot erector spinae plane block in paediatric video-assisted thoracoscopic surgeries. We had 5 patients aged 2-8 years with right-sided empyema, who were taken up for video-assisted thoracoscopic surgery decortication, and 2 patients aged 1-4 years with congenital diaphragmatic hernia (CDH) for video-assisted thoracoscopic surgery CDH repair. After induction and intubation, using high-frequency straight ultrasound probe, an erector spinae plane catheter was inserted and the local anaesthetic agent was administered. The patients were monitored for signs of effective analgesia. Post-extubation continuous erector spinae plane block was continued for 48 hours using bupivacaine and fentanyl. All patients had excellent postoperative analgesia for more than 48 hours. There were no side effects like motor block, nausea, vomiting, or respiratory depression. Continuous erector spinae plane block provides excellent analgesia in paediatric patients undergoing video-assisted thoracoscopic surgery, causing minimal side effects. Further, a prospective randomized control trial is suggested to establish the efficacy of this block in paediatric video-assisted thoracoscopic surgeries.

Loss of dlx5a/dlx6a Locus Alters Non-Canonical Wnt Signaling and Meckel's Cartilage Morphology.

The dlx genes encode transcription factors that establish a proximal-distal polarity within neural crest cells to bestow a regional identity during craniofacial development. The expression regions of dlx paralogs are overlapping yet distinct within the zebrafish pharyngeal arches and may also be involved in progressive morphologic changes and organization of chondrocytes of the face. However, how each dlx paralog of dlx1a, dlx2a, dlx5a and dlx6a affects craniofacial development is still largely unknown. We report here that the average lengths of the Meckel's, palatoquadrate and ceratohyal cartilages in different dlx mutants were altered. Mutants for dlx5a-/- and dlx5i6-/-, where the entire dlx5a/dlx6a locus was deleted, have the shortest lengths for all three structures at 5 days post fertilization (dpf). This phenotype was also observed in 14 dpf larvae. Loss of dlx5i6 also resulted in increased proliferation of neural crest cells and expression of chondrogenic markers. Additionally, altered expression and function of non-canonical Wnt signaling were observed in these mutants suggesting a novel interaction between dlx5i6 locus and non-canonical Wnt pathway regulating ventral cartilage morphogenesis.

Knock-out of vasotocin reduces reproductive success in female zebrafish, Danio rerio.

The vertebrate nonapeptide vasotocin/vasopressin is evolutionarily highly conserved and acts as neuromodulator and endocrine/paracrine signaling molecule. Circumstantial and mechanistic evidence from pharmacological manipulations of the vasotocin system in several teleost fishes suggest sex- and species-specific reproductive roles of vasotocin. While effects of vasotocin on teleost reproductive physiology involve both courtship behaviors and the regulation of the hypothalamic-pituitary-gonadal (HPG) axes, comprehensive studies investigating behavioral and physiological reproductive consequences of genetic ablation of vasotocin in a genetically tractable fish model, such as the zebrafish, are currently lacking. Here, we report the generation of homozygous CRISPR/Cas9-based vasotocin gene knock-out zebrafish. Breeding pairs of vasotocin knock-out fish produce significantly fewer fertilized eggs per clutch compared to wildtype fish, an effect coincident with reduced female quivering courtship behavior. Crossbreeding experiments reveal that this reproductive phenotype is entirely female-dependent, as vasotocin-deficient males reproduce normally when paired with female wild-type fish. Histological analyses of vasotocin knock-out ovaries revealed an overall reduction in oocytes and differential distribution of oocyte maturation stages, demonstrating that the reproductive phenotype is linked to oocyte maturation and release. Ovarian hormone quantification and gene expression analysis in mutant fish indicated reduced synthesis of Prostaglandin F2α, a hormone involved in ovarian maturation, egg release and regulation of female courtship behavior in some cyprinids. However, acute injection of vasotocin did not rescue the female mutant reproductive phenotype, suggesting a contribution of organizational effects of vasotocin. Together, this study provides further support for emerging roles of vasotocin in female teleost reproduction in an important teleost model species.

Plasmodium Iron-Sulfur [Fe-S] cluster assembly protein Dre2 as a plausible target of Artemisinin: Mechanistic insights derived in a prokaryotic heterologous system.

Iron-sulfur (Fe-S) cluster containing proteins have been assigned roles in various essential cellular processes, such as regulation of gene expression, electron transfer, sensing of oxygen and balancing free radical chemistry. However, their role as the drug target remains sparse. Recently the screening of protein alkylation targets for artemisinin in Plasmodium falciparum led to identification of Dre2, a protein involved in redox mechanism for the cytoplasmic Fe-S cluster assembly in different organisms. In the present study, to further explore the interaction between artemisinin and Dre2, we have expressed the Dre2 protein of both P. falciparum and P. vivax in E. coli. The opaque brown colour of the IPTG induced recombinant Plasmodium Dre2 bacterial pellet, suggested iron accumulation as confirmed by the ICP-OES analysis. In addition, overexpression of rPvDre2 in E. coli reduced its viability, growth and increased the ROS levels of bacterial cells, which in turn led to an increase in expression of stress response genes of E. coli such as recA, soxS, mazF. Moreover, the overexpression of rDre2 induced cell death could be rescued by treatment with Artemisinin derivatives suggesting their interaction. The interaction between DHA and PfDre2 was later demonstrated by CETSA and microscale thermophoresis. Overall, this study suggests that Dre2 is the probable target of Artemisinin and the antimalarial activity of DHA/Artemether could also be due to yet unidentified molecular mechanism altering the Dre2 activity in addition to inducing DNA and protein damage.

Novel mutations in the antifolate drug resistance marker genes among Plasmodium vivax isolates exhibiting severe manifestations.

Plasmodium vivax is the predominant species of the human malaria parasite present in the Indian subcontinent. There have been recent reports on Chloroquine (CQ) resistance and severe manifestations shown by P. vivax from different regions of the world including India. This study focuses on Bikaner, India where during the last few years there have been continuous reports of severe manifestations by both Plasmodium falciparum and P. vivax. This region has a widespread use of Chloroquine and Sulfadoxine-Pyrimethamine for the treatment of malaria, but the resistance profiles of these drugs are not available. We report here the profile of mutations in marker genes associated with Chloroquine and antifolate drug resistance among the P. vivax parasites obtained from patients with severe (n=30) and non-severe (n=48) manifestations from this region. Most isolates showed the wild type alleles for both the Chloroquine and antifolate resistance markers (P<0.0005). Except for one isolate showing Y976F mutation in the Pvmdr-1 gene, no reported mutation was observed in the Pvmdr-1 or Pvcrt gene. This is in accordance with the fact that till date no Chloroquine resistance has been reported from this region. However, the single isolate with a mutation in Pvmdr-1 may suggest the beginning of the trend towards decreased susceptibility to Chloroquine. The frequency of PvDHFR-PvDHPS two locus mutations was higher among the patients showing severe manifestations than the patient group with non-severe (uncomplicated) malaria (P<0.003). None of the parasites from patients with uncomplicated P. vivax malaria showed the mutant PvDHPS genotype. Novel mutations in PvDHFR (S117H) and PvDHPS (F365L, D459A and M601I) were observed only in the parasite population obtained from patients exhibiting severe complications. Preliminary homology modeling and molecular docking studies predicted that these mutations apparently do not have any effect on the binding of the drug molecule to the enzyme. However, the presence of novel mutations in the PvDHPS gene indicate a degree of polymorphism of this molecule which is in contrast to available published information.

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish.

AIM: Although zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1-adrenergic receptor (AR) in the regulation of heart rate in zebrafish. METHODS: CRISPR-Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1-/- line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR. RESULTS: Compared with genetically matched wild-types (adrb1+/+ ), adrb1-/- larvae exhibited ~20 beats min-1 lower heart rate, measured from 2 to 21 days post-fertilization (dpf). Nevertheless, adrb1-/- larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß-AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2 ) at 5 dpf, but tachycardia was blunted in adrb1-/- larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1-/- larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1-/- larval hearts. CONCLUSION: Despite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1-/- line. The chronotropic effects of adrenergic stimulation persist in adrb1-/- zebrafish, likely due to the upregulation of other ß-AR subtypes.

Epidemiology of Traumatic Posterior Hip Instability in the National Football League.

BACKGROUND: There is a paucity of literature regarding injury incidence, mechanism, and return to play in National Football League (NFL) players who have sustained traumatic posterior hip instability. PURPOSE: To describe the incidence of traumatic posterior hip instability and the rate of return to play in NFL players across 18 seasons. STUDY DESIGN: Descriptive epidemiology study. METHODS: We retrospectively assessed all traumatic posterior hip dislocations/subluxations that occurred during football-related activities in the NFL seasons from 2000 through 2017. Player demographics and injury data (injury mechanism, season of injury, treatment, days missed, and return to play time) were collected from all 32 NFL teams prospectively through a leaguewide electronic health record system. Descriptive statistics are presented. RESULTS: Across the 18 NFL seasons, 16 posterior hip instability injuries in 14 players were reported, with a maximum incidence of 4 (25%) in 2013. Posterior hip instability was predominantly sustained by offensive players (64.3%), with tight ends being the most affected (31.3%). Half of the injuries occurred during the regular season, 43.8% in the preseason, and 6.2% in the offseason. Of all injuries, 37.5% were noncontact, while 56.3% involved contact (direct or indirect), and 6.2% were of unknown mechanism. Among noncontact injuries, 66.7% occurred during cutting and change of direction while sprinting. The time of return to full participation was documented for 11 of the 16 reported injuries (68.8%); among them, the mean time loss was 136.7 ± 83.8 days-143.3 ± 99.6 days if the player underwent surgery (n = 4) and 116.7 ± 76.2 days missed by players without surgery (n = 6)-the treatment modality was unknown in 1 player. CONCLUSION: Although the incidence of traumatic posterior hip instability during the study period was low, all injured athletes missed time from football activities and competitions. Injuries that required surgery led to more missed time than those that did not. Ongoing research to understand risk factors and mechanisms of this injury, in conjunction with improvements to prevention and rehabilitation protocols, is necessary to ensure the safety of professional American football players.

Rethinking the routine: Preoperative laboratory testing among American Society of Anesthesiologists class 1 and 2 patients before low-risk ambulatory surgery in the 2017 National Surgical Quality Improvement Program cohort.

BACKGROUND: Routine preoperative laboratory testing is not recommended for American Society of Anesthesiologists classification 1 or 2 patients before low-risk ambulatory surgery. METHODS: The 2017 National Surgical Quality Improvement Program data set was retrospectively queried for American Society of Anesthesiologists class 1 and 2 patients who underwent low-risk, elective outpatient anorectal, breast, endocrine, gynecologic, hernia, otolaryngology, oral-maxillofacial, orthopedic, plastic/reconstructive, urologic, and vascular operations. Preoperative laboratory testing was defined as any chemistry, hematology, coagulation, or liver function studies obtained ≤30 days preoperatively. Demographics, comorbidities, and outcomes were compared between those with and without testing. The numbers needed to test to prevent serious morbidity or any complication were calculated. Laboratory testing costs were estimated using Centers for Medicare and Medicaid Services data. RESULTS: Of 111,589 patients studied, 57,590 (51.6%) received preoperative laboratory testing; 26,709 (46.4%) had at least 1 abnormal result. Factors associated with receiving preoperative laboratory testing included increasing age, female sex, non-White race/ethnicity, American Society of Anesthesiologists class 2, diabetes, dyspnea, hypertension, obesity, and steroid use. Mortality did not differ between patients with and without testing. The complication rate was 2.5% among tested patients and 1.7% among patients without tests (P < .01). The numbers needed to test was 599 for serious morbidity and 133 for any complication. An estimated $373 million annually is spent on preoperative laboratory testing in this population. CONCLUSION: Despite American Society of Anesthesiologists guidelines, a majority of American Society of Anesthesiologists class 1 and 2 patients undergo preoperative laboratory testing before elective low-risk outpatient surgery. The differences in the rates of complications between patients with and without testing is low. Preoperative testing should be used more judiciously in this population, which may lead to cost savings.