Plasma Cell Differentiation, Antibody Quality, and Initial Germinal Center B Cell Population Depend on Glucose Influx Rate.

Serum Ab concentrations, selection for higher affinity BCRs, and generation of higher Ab affinities are important elements of immune response optimization and functions of germinal center (GC) reactions. B cell proliferation requires nutrients to support the anabolism inherent in clonal expansion. Glucose usage by mouse GC B cells has been reported to contribute little to their energy needs, with questions raised as to whether glucose uptake or glycolysis increases in GC B cells compared with their naive precursors. Indeed, metabolism can be highly flexible, such that supply shortage along one pathway may be compensated by increased flux on others. We now show that reduction of the glucose transporter GLUT1 in mice after establishment of a preimmune B cell repertoire, even after initiation of the GC B cell gene expression program, decreased initial GC B cell population numbers, affinity maturation, and plasma cell outputs. Glucose oxidation was heightened in GC B cells, but this hexose flowed more into the pentose phosphate pathway, whose activity was important in controlling reactive oxygen species (ROS) and Ab-secreting cell production. In modeling how glucose usage by B cells promotes the Ab response, the control of ROS appeared insufficient. Surprisingly, the combination of galactose, which mitigated ROS, with provision of mannose, an efficient precursor to glycosylation, supported robust production of and normal Ab secretion by Ab-secreting cells under glucose-free conditions. Collectively, the findings indicate that GCs depend on normal glucose influx, especially in plasma cell production, but reveal an unexpected metabolic flexibility in hexose requirements.

Complementing T Cells' Functions: Bringing in Metabolism Matters.

Components of the complement system act directly on T cells to alter conventional and regulatory T cell subsets. In this issue of Immunity, Kolev, Dimeloe, Le Friec et al. (2015) provide evidence of a mechanism by which the complement stimulates sustained mTORC1 activation and regulates cellular metabolism.

Impact of COVID-19 pandemic on interhospital transfer of patients with major trauma in Korea: a retrospective cohort study.

BACKGROUND: Interhospital transfer (IHT) is necessary for providing ultimate care in the current emergency care system, particularly for patients with severe trauma. However, studies on IHT during the pandemic were limited. Furthermore, evidence on the effects of the coronavirus disease 2019 (COVID-19) pandemic on IHT among patients with major trauma was lacking. METHOD: This retrospective cohort study was conducted in an urban trauma center (TC) of a tertiary academic affiliated hospital in Daegu, Korea. The COVID-19 period was defined as from February 1, 2020 to January 31, 2021, whereas the pre-COVID-19 period was defined as the same duration of preceding span. Clinical data collected in each period were compared. We hypothesized that the COVID-19 pandemic negatively impacted IHT. RESULTS: A total of 2,100 individual patients were included for analysis. During the pandemic, the total number of IHTs decreased from 1,317 to 783 (- 40.5%). Patients were younger (median age, 63 [45-77] vs. 61[44-74] years, p = 0.038), and occupational injury was significantly higher during the pandemic (11.6% vs. 15.7%, p = 0.025). The trauma team activation (TTA) ratio was higher during the pandemic both on major trauma (57.3% vs. 69.6%, p = 0.006) and the total patient cohort (22.2% vs. 30.5%, p < 0.001). In the COVID-19 period, duration from incidence to the TC was longer (218 [158-480] vs. 263[180-674] minutes, p = 0.021), and secondary transfer was lower (2.5% vs. 0.0%, p = 0.025). CONCLUSION: We observed that the total number of IHTs to the TC was reduced during the COVID-19 pandemic. Overall, TTA was more frequent, particularly among patients with major trauma. Patients with severe injury experienced longer duration from incident to the TC and lesser secondary transfer from the TC during the COVID-19 pandemic.

AMPKα1 in B Cells Dampens Primary Antibody Responses yet Promotes Mitochondrial Homeostasis and Persistence of B Cell Memory.

Emerging evidence indicates that metabolic programs regulate B cell activation and Ab responses. However, the metabolic mediators that support the durability of the memory B cell and long-lived plasma cell populations are not fully elucidated. Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved serine/threonine kinase that integrates cellular energy status and nutrient availability to intracellular signaling and metabolic pathways. In this study, we use genetic mouse models to show that loss of ΑMPKα1 in B cells led to a weakened recall Ab response associated with a decline in the population of memory-phenotype B cells. AMPKα1-deficient memory B lymphocytes exhibited aberrant mitochondrial activity, decreased mitophagy, and increased lipid peroxidation. Moreover, loss of AMPKα1 in B lymphoblasts was associated with decreased mitochondrial spare respiratory capacity. Of note, AMPKα1 in B cells was dispensable for stability of the bone marrow-resident, long-lived plasma cell population, yet absence of this kinase led to increased rates of Ig production and elevated serum Ab concentrations elicited by primary immunization. Collectively, our findings fit a model in which AMPKα1 in B cells supports recall function of the memory B cell compartment by promoting mitochondrial homeostasis and longevity but restrains rates of Ig production.

Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.

Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class, both cell-autonomous and extrinsic metabolic programming have emerged as modulators of T-cell-mediated immunity. Here we show in mice that GC light zones are hypoxic, and that low oxygen tension () alters B cell physiology and function. In addition to reduced proliferation and increased B cell death, low impairs antibody class switching to the pro-inflammatory IgG2c antibody isotype by limiting the expression of activation-induced cytosine deaminase (AID). Hypoxia induces HIF transcription factors by restricting the activity of prolyl hydroxyl dioxygenase enzymes, which hydroxylate HIF-1α and HIF-2α to destabilize HIF by binding the von Hippel-Landau tumour suppressor protein (pVHL). B-cell-specific depletion of pVHL leads to constitutive HIF stabilization, decreases antigen-specific GC B cells and undermines the generation of high-affinity IgG, switching to IgG2c, early memory B cells, and recall antibody responses. HIF induction can reprogram metabolic and growth factor gene expression. Sustained hypoxia or HIF induction by pVHL deficiency inhibits mTOR complex 1 (mTORC1) activity in B lymphoblasts, and mTORC1-haploinsufficient B cells have reduced clonal expansion, AID expression, and capacities to yield IgG2c and high-affinity antibodies. Thus, the normal physiology of GCs involves regional variegation of hypoxia, and HIF-dependent oxygen sensing regulates vital functions of B cells. We propose that the restriction of oxygen in lymphoid organs, which can be altered in pathophysiological states, modulates humoral immunity.

Hypoxia-inducible factors in CD4+ T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity.

T cell help in humoral immunity includes interactions of B cells with activated extrafollicular CD4+ and follicular T helper (Tfh) cells. Each can promote antibody responses but Tfh cells play critical roles during germinal center (GC) reactions. After restimulation of their antigen receptor (TCR) by B cells, helper T cells act on B cells via CD40 ligand and secreted cytokines that guide Ig class switching. Hypoxia is a normal feature of GC, raising questions about molecular mechanisms governing the relationship between hypoxia response mechanisms and T cell help to antibody responses. Hypoxia-inducible factors (HIF) are prominent among mechanisms that mediate cellular responses to limited oxygen but also are induced by lymphocyte activation. We now show that loss of HIF-1α or of both HIF-1α and HIF-2α in CD4+ T cells compromised essential functions in help during antibody responses. HIF-1α depletion from CD4+ T cells reduced frequencies of antigen-specific GC B cells, Tfh cells, and overall antigen-specific Ab after immunization with sheep red blood cells. Compound deficiency of HIF-1α and HIF-2α led to humoral defects after hapten-carrier immunization. Further, HIF promoted CD40L expression while restraining the FoxP3-positive CD4+ cells in the CXCR5+ follicular regulatory population. Glycolysis increases T helper cytokine expression, and HIF promoted glycolysis in T helper cells via TCR or cytokine stimulation, as well as their production of cytokines that direct antibody class switching. Indeed, IFN-γ elaboration by HIF-deficient in vivo-generated Tfh cells was impaired. Collectively, the results indicate that HIF transcription factors are vital components of the mechanisms of help during humoral responses.

Discovering New Lipidomic Features Using Cell Type Specific Fluorophore Expression to Provide Spatial and Biological Specificity in a Multimodal Workflow with MALDI Imaging Mass Spectrometry.

Identifying the spatial distributions of biomolecules in tissue is crucial for understanding integrated function. Imaging mass spectrometry (IMS) allows simultaneous mapping of thousands of biosynthetic products such as lipids but has needed a means of identifying specific cell-types or functional states to correlate with molecular localization. We report, here, advances starting from identity marking with a genetically encoded fluorophore. The fluorescence emission data were integrated with IMS data through multimodal image processing with advanced registration techniques and data-driven image fusion. In an unbiased analysis of spleens, this integrated technology enabled identification of ether lipid species preferentially enriched in germinal centers. We propose that this use of genetic marking for microanatomical regions of interest can be paired with molecular information from IMS for any tissue, cell-type, or activity state for which fluorescence is driven by a gene-tracking allele and ultimately with outputs of other means of spatial mapping.

mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

Ample evidence indicates that nutrient concentrations in extracellular milieux affect signaling mediated by environmental sensor proteins. For instance, the mechanistic target of rapamycin (mTOR) is reduced during protein malnutrition and is known to be modulated by concentrations of several amino acids when in a multiprotein signaling complex that contains regulatory-associated protein of mTOR. We hypothesized that a partial decrease in mTOR complex 1 (mTORC1) activity intrinsic to B-lineage cells would perturb lymphocyte development or function, or both. We show that a cell-intrinsic decrease in mTORC1 activity impacted developmental progression, antigen receptor repertoire, and function along the B lineage. Thus, preimmune repertoires of B-lineage cells were altered in the marrow and periphery in a genetic model of regulatory-associated protein of mTOR haplo-insufficiency. An additional role for mTORC1 was revealed when a B-cell antigen receptor transgene was found to circumvent the abnormal B-cell development: haploinsufficient B cells were profoundly impaired in responses to antigen in vivo. Collectively, our findings indicate that mTORC1 serves as a rheostat that shapes differentiation along the B lineage, the preimmune repertoire, and antigen-driven selection of mature B cells. The findings also reveal a range in the impact of this nutrient sensor on activity-response relationships for distinct endpoints.-Raybuck, A. L., Lee, K., Cho, S. H., Li, J., Thomas, J. W., Boothby, M. R. mTORC1 as a cell-intrinsic rheostat that shapes development, preimmune repertoire, and function of B lymphocytes.

B Cell-Intrinsic mTORC1 Promotes Germinal Center-Defining Transcription Factor Gene Expression, Somatic Hypermutation, and Memory B Cell Generation in Humoral Immunity.

B lymphocytes migrate among varied microenvironmental niches during diversification, selection, and conversion to memory or Ab-secreting plasma cells. Aspects of the nutrient milieu differ within these lymphoid microenvironments and can influence signaling molecules such as the mechanistic target of rapamycin (mTOR). However, much remains to be elucidated as to the B cell-intrinsic functions of nutrient-sensing signal transducers that modulate B cell differentiation or Ab affinity. We now show that the amino acid-sensing mTOR complex 1 (mTORC1) is vital for induction of Bcl6-a key transcriptional regulator of the germinal center (GC) fate-in activated B lymphocytes. Accordingly, disruption of mTORC1 after B cell development and activation led to reduced populations of Ag-specific memory B cells as well as plasma cells and GC B cells. In addition, induction of the germ line transcript that guides activation-induced deaminase in selection of the IgG1 H chain region during class switching required mTORC1. Expression of the somatic mutator activation-induced deaminase was reduced by a lack of mTORC1 in B cells, whereas point mutation frequencies in Ag-specific GC-phenotype B cells were only halved. These effects culminated in a B cell-intrinsic defect that impacted an antiviral Ab response and drastically impaired generation of high-affinity IgG1. Collectively, these data establish that mTORC1 governs critical B cell-intrinsic mechanisms essential for establishment of GC differentiation and effective Ab production.

Accuracy of machine learning for differentiation between optic neuropathies and pseudopapilledema.

BACKGROUND: This study is to evaluate the accuracy of machine learning for differentiation between optic neuropathies, pseudopapilledema (PPE) and normals. METHODS: Two hundred and ninety-five images of optic neuropathies, 295 images of PPE, and 779 control images were used. Pseudopapilledema was defined as follows: cases with elevated optic nerve head and blurred disc margin, with normal visual acuity (> 0.8 Snellen visual acuity), visual field, color vision, and pupillary reflex. The optic neuropathy group included cases of ischemic optic neuropathy (177), optic neuritis (48), diabetic optic neuropathy (17), papilledema (22), and retinal disorders (31). We compared four machine learning classifiers (our model, GoogleNet Inception v3, 19-layer Very Deep Convolution Network from Visual Geometry group (VGG), and 50-layer Deep Residual Learning (ResNet)). Accuracy and area under receiver operating characteristic curve (AUROC) were analyzed. RESULTS: The accuracy of machine learning classifiers ranged from 95.89 to 98.63% (our model: 95.89%, Inception V3: 96.45%, ResNet: 98.63%, and VGG: 96.80%). A high AUROC score was noted in both ResNet and VGG (0.999). CONCLUSIONS: Machine learning techniques can be combined with fundus photography as an effective approach to distinguish between PPE and elevated optic disc associated with optic neuropathies.

PARP-14 combines with tristetraprolin in the selective posttranscriptional control of macrophage tissue factor expression.

Tissue factor (TF) (CD142) is a 47 kDa transmembrane cell surface glycoprotein that triggers the extrinsic coagulation cascade and links thrombosis with inflammation. Although macrophage TF expression is known to be regulated at the RNA level, very little is known about the mechanisms involved. Poly(adenosine 5'-diphosphate [ADP]-ribose)-polymerase (PARP)-14 belongs to a family of intracellular proteins that generate ADP-ribose posttranslational adducts. Functional screening of PARP-14-deficient macrophages mice revealed that PARP-14 deficiency leads to increased TF expression and functional activity in macrophages after challenge with bacterial lipopolysaccharide. This was related to an increase in TF messenger RNA (mRNA) stability. Ribonucleoprotein complex immunoprecipitation and biotinylated RNA pull-down assays demonstrated that PARP-14 forms a complex with the mRNA-destabilizing protein tristetraprolin (TTP) and a conserved adenylate-uridylate-rich element in the TF mRNA 3' untranslated region. TF mRNA regulation by PARP-14 was selective, as tumor necrosis factor (TNF)α mRNA, which is also regulated by TTP, was not altered in PARP-14 deficient macrophages. Consistent with the in vitro data, TF expression and TF activity, but not TNFα expression, were increased in Parp14(-/-) mice in vivo. Our study provides a novel mechanism for the posttranscriptional regulation of TF expression, indicating that this is selectively regulated by PARP-14.

Requirement for Rictor in homeostasis and function of mature B lymphoid cells.

The mammalian target of rapamycin (mTOR), an essential serine/threonine kinase, functions in biochemically distinct multiprotein complexes, but little is known about roles of the complexes in B cells. The acutely rapamycin-sensitive mTOR complex 1 (mTORC1) is defined by a core subunit Raptor, whereas mTORC2 lacks Raptor and, instead, has Rictor and SIN1 as distinct essential components. We now show that homeostasis and function of B cells require Rictor. Conditional deletion of Rictor before lymphoid specification impaired generation of mature follicular, marginal zone, and B1a B lymphocytes. Induced inactivation in adult mice caused cell-autonomous defects in B lymphoid homeostasis and antibody responses in vivo, along with affecting plasma cells in bone marrow. Survival of B lymphocytes depended on Rictor, which was vital for normal induction of prosurvival genes, suppression of proapoptotic genes, nuclear factor κB induction after B-cell receptor stimulation, and B-cell activating factor-induced nuclear factor κB2/p52 generation. Collectively, the findings provide evidence that mTOR signaling affects survival and proliferation of mature B lymphocytes, and establish Rictor as an important signal relay in B-cell homeostasis, fate, and functions.

STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.

CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ. IL-4-producing Th2 effector cells give rise to a long-lived memory population committed to reactivation of the Th2 cytokine gene expression program. However, reactivation of these effector-derived cells under Th1-skewing conditions leads to production of IFN-γ along with IL-4 in the same cell. We now show that this flexibility ("plasticity") of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells. Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells. Taken together, our data suggest a model in which the expression of IFN-γ by Th2-derived memory cells involves attenuation of epigenetic repression in memory Th2 cells, combined with Th1-polarizing signals after their recall activation.

B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an intracellular (ADP-ribosyl)transferase.

The capacity to achieve sufficient concentrations of Ag-specific Ab of the appropriate isotypes is a critical component of immunity that requires efficient differentiation and interactions of Ag-specific B and Th cells along with dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of mammalian proteins to influence cell physiology and adaptive immunity. However, little is known about biological functions of intracellular mammalian mono(ADP-ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP-ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency reduced the levels of Th17 cells and CD103⁺ DCs, which are implicated in IgA regulation. PARP14 enhanced the expression of RORα, Runx1, and Smad3 after T cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17 differentiation. Collectively, the findings show that PARP14 influences the class distribution, affinity repertoire, and recall capacity of Ab responses in mice, as well as provide direct evidence of the requirement for protein mono-ADP-ribosylation in Th cell differentiation.

Sludge Reduction by H2O2 Oxidation with Fe/MgO Catalyst.

This study aimed to determine whether catalytic pretreatment can be used as a method to reduce the amount of wastewater sludge. In this study, H2O2 oxidation in the presence of a heterogeneous Fe/MgO catalyst was added to the pretreatment step. Initially a laboratory-scale test showed a TCOD (total chemical oxygen demand) was reduced 27.4% during catalytic oxidation compared to 2.1% in a catalyst-free option. Catalytic pretreatment was then evaluated in a bench-scale flow-loop test. Two bench systems were composed of identical serial processes that included anaerobic digestion, aerobic digestion, and coagulating sedimentation. The only difference between the two processes was whether catalytic pretreatment of sediment sludge was used or not. Results showed that catalyst-free oxidation TCOD gradually increased from 4200 to 7800 mg/L while catalytic oxidation maintained TCOD values at 4200 ± 200 mg/L. In addition, catalytic pretreatment reduced total nitrogen from 46.9 to 41.0 mg/L and phosphate from 3.1 to 2.3 mg/L.

Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family.

Poly(ADP-ribose)polymerase (PARP)14--a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs--is an ADP ribosyltransferase that interacts with Stat6, enhances induction of certain genes by IL-4, and is expressed in B lymphocytes. We now show that IL-4 enhancement of glycolysis in B cells requires PARP14 and that this process is central to a role of PARP14 in IL-4-induced survival. Thus, enhancements of AMP-activated protein kinase activity restored both IL-4-induced glycolytic activity in Parp14(-/-) B cells and prosurvival signaling by this cytokine. Suppression of apoptosis is central to B-lymphoid oncogenesis, and elevated macro-PARP expression has been correlated with lymphoma aggressiveness. Strikingly, PARP14 deficiency delayed B lymphomagenesis and reversed the block to B-cell maturation driven by the Myc oncogene. Collectively, these findings reveal links between a mammalian ADP ribosyltransferase, cytokine-regulated metabolic activity, and apoptosis; show that PARP14 influences Myc-induced oncogenesis; and suggest that the PARP14-dependent capacity to increase cellular metabolic rates may be an important determinant of lymphoma pathobiology.

Plasma cell differentiation, antibody quality, and initial germinal center B cell population depend on glucose influx rate.

Antibody secretion into sera, selection for higher affinity BCR, and the generation of higher Ab affinities are important elements of immune response optimization, and a core function of germinal center reactions. B cell proliferation requires nutrients to support the anabolism inherent in clonal expansion. Glucose usage by GC B cells has been reported to contribute little to their energy needs, with questions raised as to whether or not glucose uptake or glycolysis increases in GC B cells compared to their naïve precursors. Indeed, metabolism can be highly flexible, such that supply shortage along one pathway may be compensated by increased flux on others. We now show that elimination of the glucose transporter GLUT1 after establishment of a pre-immune B cell repertoire, even after initiation of the GC B cell gene expression program, decreased initial GC B cell population numbers, affinity maturation, and PC outputs. Glucose oxidation was heightened in GC B cells, but this hexose flowed more into the pentose phosphate pathway (PPP), whose activity was important in controlling reactive oxygen (ROS) and ASC production. In modeling how glucose usage by B cells promotes the Ab response, the control of ROS appeared insufficient. Surprisingly, the combination of galactose, which mitigated ROS, with provision of mannose - an efficient precursor to glycosylation - supported robust production of and normal Ab secretion by ASC under glucose-free conditions. Collectively, the findings indicate that GC depend on normal glucose influx, especially in PC production, but reveal an unexpected metabolic flexibility in hexose requirements. KEY POINTS: Glucose influx is critical for GC homeostasis, affinity maturation and the generation of Ab-secreting cells.Plasma cell development uses the Pentose Phosphate Pathway, and hexose sugars maintain redox homeostasis.PCs can develop and achieve robust Ab secretion in the absence of glucose using a combination of hexose alternatives.

Poly(ADP-ribose) polymerase 9 mediates early protection against Mycobacterium tuberculosis infection by regulating type I IFN production.

The ADP ribosyltransferases (PARPs 1-17) regulate diverse cellular processes, including DNA damage repair. PARPs are classified on the basis of their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). Although PARP9 mRNA expression is significantly increased in progressive tuberculosis (TB) in humans, its participation in host immunity to TB is unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme was upregulated during TB in humans and mice and provide evidence of a critical modulatory role for PARP9 in DNA damage, cyclic GMP-AMP synthase (cGAS) expression, and type I IFN production during TB. Thus, Parp9-deficient mice were susceptible to Mycobacterium tuberculosis infection and exhibited increased TB disease, cGAS and 2'3'-cyclic GMP-AMP (cGAMP) expression, and type I IFN production, along with upregulation of complement and coagulation pathways. Enhanced M. tuberculosis susceptibility is type I IFN dependent, as blockade of IFN α receptor (IFNAR) signaling reversed the enhanced susceptibility of Parp9-/- mice. Thus, in sharp contrast to PARP9 enhancement of type I IFN production in viral infections, this member of the MAR family plays a protective role by limiting type I IFN responses during TB.

Risk factors of trauma-induced thrombotic microangiopathy-like syndrome: A retrospective analysis.

Patients with trauma may develop thrombocytopenia. We encountered cases wherein patients experienced symptoms resembling thrombotic microangiopathies (TMAs) following severe trauma. As the condition of these patients did not meet the diagnostic criteria of thrombotic thrombocytopenic purpura and there was no mention of trauma among the several causes of TMAs, it was termed as "trauma-induced thrombotic microangiopathy-like syndrome" (t-TMAS). In this study, we aimed to analyze the risk factors that may affect the incidence of t-TMAS in patients with severe trauma. This retrospective study was conducted in the trauma intensive care unit at the Kyungpook National University Hospital between January 2018 and December 2019. The medical records of 1164 of the 1392 enrolled participants were analyzed. To assess the risk factors of t-TMAS, we analyzed age, sex, mechanism of trauma, abbreviated injury scale (AIS) score, injury severity score (ISS), hematological examination, and red blood cell volume transfused in 24 hours. Among the 1164 patients, 20 (1.7%) were diagnosed with t-TMAS. The univariate analysis revealed higher age, ISS, and myoglobin, lactate, creatine kinase-myocardial band (on admission), creatine phosphokinase, lactate dehydrogenase (LDH), and lactate (day 2) levels in the t-TMAS group than in the non-t-TMAS group. The red blood cell volume transfused in 24 hours was higher in the t-TMAS group than in the non-t-TMAS group. t-TMAS was more common in patients with injuries in the chest, abdomen, and pelvis (AIS score ≥3) than in those with head injuries (AIS score ≥3) alone. The higher the sum of AIS scores of the chest, abdomen, and pelvis injuries, the higher the incidence of t-TMAS. Multivariate analysis revealed age, ISS, and LDH level (day 2) to be independent predictors of t-TMAS. Trauma surgeons should consider the possibility of t-TMAS if thrombocytopenia persists without any evidence of bleeding, particularly among older patients with multiple severe torso injuries who have high LDH levels on day 2. Early diagnosis and treatment of t-TMAS could improve patients' prognosis.

Laparoscopic repair of colonoscopy-induced adult Bochdalek hernia: Case report.

INTRODUCTION: Bochdalek hernias are congenital diaphragmatic malformations caused by a failure to close the pleuroperitoneal cavity in the posterolateral area. Bochdalek hernias are very rare in adult, with congenital diaphragmatic defects being even rarer. PRESENTATION OF CASE: A 35-year-old man presented to our emergency room with epigastric pain after colonoscopy. The patient had no history of trauma. Plain chest X-ray revealed bowel gas patterns and haziness in the left lower lung field. Abdominal computed tomography revealed a left diaphragmatic defect in the posterolateral area, with herniation of the omentum and colon. The patient successfully underwent laparoscopic herniorrhaphy. DISCUSSION: The diaphragm comprises fibrous tissue and muscle. Therefore, direct damage by a colonoscope is almost impossible. Normal chest X-ray as a part of a health screening was performed 9 days prior to admission, and the size of the diaphragmatic defect could be covered by the spleen; therefore, the patient was considered hernia-free for over 30 years. CONCLUSION: We report a rare case of delayed Bochdalek hernia that may have been induced by the difficult insertion of a colonoscopy. Although rare, this disorder should be recognized, examined and treated appropriately to avoid complications.