Prevalence of antiphospholipid autoantibodies associated with biologics treatment for psoriasis.

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.

The optimal use of tildrakizumab in the elderly via improvement of Treg function and its preventive effect of psoriatic arthritis.

Introduction: As a form of precision medicine, this study aimed to investigate the specific patient population that would derive the greatest benefit from tildrakizumab, as well as the mechanism of action and efficacy of tildrakizumab in reducing the occurrence of psoriatic arthritis (PsA). Methods: To achieve this, a multi-center, prospective cohort study was conducted, involving a population of 246 psoriasis patients who had not received any systemic therapy or topical finger therapy between January 2020 and April 2023. Two independent clinicians, who were blinded to the study, analyzed nailfold capillary (NFC) abnormalities, such as nailfold bleeding (NFB) and enlarged capillaries, as well as the incidence of new PsA. Additionally, the factors that determined the response of psoriasis after seven months of tildrakizumab treatment were examined. The study also examined the quantity and role of regulatory T cells (Tregs) and T helper 17 cells both pre- and post-treatment. Results: The severity of psoriasis, as measured by the Psoriasis Area and Severity Index (PASI), was found to be more pronounced in the tildrakizumab group (n=20) in comparison to the topical group (n=226). At 7 months after tildrakizumab treatment, multivariate analysis showed that those 65 years and older had a significantly better response to treatment in those achieved PASI clear or PASI 2 or less (Likelihood ratio (LR) 16.15, p<0.0001; LR 6. 16, p=0.01). Tildrakizumab improved the number and function of Tregs, which had been reduced by aging. Tildrakizumab demonstrated significant efficacy in improving various pathological factors associated with PsA. These factors include the reduction of NFB, enlargement of capillaries, and inhibition of PsA progression. The hazard ratio for progression to PsA was found to be 0.06 (95% confidence interval: 0.0007-0.46, p=0.007), indicating a substantial reduction in the risk of developing PsA. Discussion: Tildrakizumab's effectiveness in improving skin lesions can be attributed to its ability to enhance the number and function of Tregs, which are known to decline with age. Furthermore, the drug's positive impact on NFB activity and capillary enlargement, both of which are recognized as risk factors for PsA, further contribute to its inhibitory effect on PsA progression.

Utility of nailfold capillary assessment for predicting pustulotic arthro-osteitis in palmoplantar pustulosis based on a prospective cohort study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known. OBJECTIVE: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP. METHODS: We conducted a prospective cohort study in a population of 102 PPP patients. Correlations of NFC abnormalities, including nailfold bleeding and enlarged capillaries, with the prevalence of PAO, the incidence of new PAO, and serum levels of cytokines were analyzed. RESULTS: Detailed examination revealed that of 102 PPP patients, 52 without PAO and 50 with PAO. Both nailfold bleeding and enlarged capillaries were significantly more frequent in patients with PAO (50.0% vs 92.0%, P < .0001; 50.0% vs 94.0%, P < .0001). In addition, PPP patients without PAO were prospectively observed before they developed PAO (mean 28 months [1-52 months]). Multivariate analysis suggested that these NFC abnormalities were predictors of PAO development (hazard ratio 3.37, 95% confidence interval 1.13-10.07; 3.37, 1.13-10.07) and guselkumab prevent PAO development (0.093, 0.012-0.76). The degree of NFC abnormalities correlated with the severity of PAO and serum cytokine levels. LIMITATIONS: All participants were Japanese. CONCLUSION: NFC abnormalities could be predictors of PAO in PPP patients, and their degree indicators of disease severity.

Extubation by supraglottic airway after lobectomy prevents cough-associated air leaks and prolonged coughing or sore throat.

OBJECTIVES: Double-lumen endobronchial tubes (DLTs) are essential for differential lung ventilation during pulmonary lobectomy, but they are more rigid, longer, larger in diameter and irritable. Coughing at extubation sometimes causes airway and lung injury, which causes severe air leaks, prolonged cough and sore throat. We examined the prevalence of cough-associated air leaks at extubation and postoperative cough or sore throat after lobectomy and evaluated the efficacy of supraglottic airway (SGA) in preventing these complications. METHODS: Patient characteristics and operative and postoperative factors data were collected from patients who underwent pulmonary lobectomy between January 2013 and March 2022. After propensity score matching, these data were compared between the SGA and DLT groups. RESULTS: A total of 1069 patients with lung cancer (SGA, 641; DLTs, 428) were enrolled and coughing at extubation occurred in 100 (23.4%) patients in the DLT group, 65 (65.0%) showed increased cough-associated air leaks at extubation and 20 (30.8%) showed prolonged air leaks. Coughing at extubation occurred in 6 (0.9%) in the SGA group. In 193 patients from each group after propensity score matching, coughing at extubation and the associated air leak increase were significantly lower in the SGA group. Visual analogue scale of postoperative cough and sore throat on postoperative days 2, 7 and 30 were significantly lower in the SGA group. CONCLUSIONS: SGA is effective and safe for preventing cough-associated air leaks and prolonged postoperative cough or sore throat at extubation following pulmonary lobectomy.

Rapid improvement of systemic sclerosis-associated intestinal pseudo-obstruction with intravenous immunoglobulin administration.

OBJECTIVES: SSc is an autoimmune disease characterized by excessive fibrosis in multiple organs, including the gastrointestinal (GI) tract. GI symptoms of SSc such as intestinal pseudo-obstruction (IPO) are often refractory to conventional intervention and can result in longer in-hospital stay or even increased mortality. We aimed to summarize the insights to date regarding the efficacy of IVIG against GI symptoms of SSc to unveil what we should focus on in future studies. METHODS: Herein we report the response of GI symptoms in three cases with SSc-myositis overlap who received IVIG administration. We also conducted a systematic literature review to summarize previous reports regarding the efficacy of IVIG upon the GI manifestations of SSc, according to the PRISMA 2020 guideline. RESULTS: The case series demonstrated remarkable and rapid improvement of GI symptoms, including IPO, after IVIG administration. The literature review revealed that previous reports also support the efficacy and safety of IVIG against GI manifestations of SSc. However, they were all retrospective studies and lacking description of the short-term outcome after IVIG administration with objective and quantitative metrics. CONCLUSION: IVIG seems to be a promising therapeutic option for the management of GI symptoms in SSc, including IPO. Investigators should focus more on short-term outcomes to properly assess the therapeutic benefit of IVIG, ideally using reliable quantitative measures in a multicentre randomized placebo-controlled setting.

Utility of nailfold capillary assessment for predicting psoriatic arthritis based on a prospective observational cohort study.

OBJECTIVES: PsA is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. METHODS: We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A and IL-23 were analysed. RESULTS: Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs 84.5%, P < 0.0001; 25.4% vs 100%, P < 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95% CI 2, 77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95% CI 1.38, 5.47 and HR 4.49, 95% CI 2.25, 8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. CONCLUSIONS: NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity.

Protective effect of a mitochondria-targeting peptide against paclitaxel-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of several anticancer agents including paclitaxel, a chemotherapeutic drug widely used in cancer treatment. CIPN deteriorates patients' quality of life and compromises cancer treatment. Dysfunction or injury of mitochondria has been suggested to be involved in the induction of this neuropathy. SS-20 is a tetrapeptide that targets mitochondria and restores mitochondrial bioenergetics. This study was aimed to examine the protective effect of SS-20 against paclitaxel-induced peripheral neuropathy using a murine model. Repeated administration of paclitaxel to mice induced peripheral neuropathy as demonstrated by the presence of mechanical allodynia and the loss of intraepidermal nerve fibers in the hind paw. Concomitant administration of SS-20 protected against the development of the neuropathy. Our results suggest that SS-20 may be a drug candidate for the prevention of CIPN.

Effects of human induced pluripotent stem cell-derived intestinal organoids on colitis-model mice.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by repeated remissions and relapses. Immunosuppressive drugs have facilitated the induction and maintenance of remission in many patients with UC. However, immunosuppressive drugs cannot directly repair impaired intestinal mucosa and are insufficient for preventing relapse. Therefore, new treatment approaches to repair the damaged epithelium in UC have been attempted through the transplantation of intestinal organoids, which can be differentiated into mucosa by embedding in Matrigel, generated from patient-derived intestinal stem cells. The method, however, poses the challenge of yielding sufficient cells for UC therapy, and patient-derived cells might already have acquired pathological changes. In contrast, human induced pluripotent stem (iPS) cells generated from healthy individuals are infinitely proliferated and can be differentiated into target cells. Recently developed human iPS cell-derived intestinal organoids (HIOs) aim to generate organoids that closely resemble the adult intestine. However, no study till date has reported HIOs injected into in vivo inflammatory models, and it remains unclear whether HIOs with cells that closely resemble the adult intestine or with intestinal stem cells retain the better ability to repair tissue in colitis. Methods: We generated two types of HIOs via suspension culture with and without small-molecule compounds: HIOs that include predominantly more intestinal stem cells [HIO (A)] and those that include predominantly more intestinal epithelial and secretory cells [HIO (B)]. We examined whether the generated HIOs engrafted in vivo and compared their ability to accelerate recovery of the damaged tissue. Results: Findings showed that the HIOs expressed intestinal-specific markers such as caudal-type homeobox 2 (CDX2) and villin, and HIOs engrafted under the kidney capsules of mice. We then injected HIOs into colitis-model mice and found that the weight and clinical score of the mice injected with HIO (A) recovered earlier than that of the mice in the sham group. Further, the production of mucus and the expression of cell proliferation markers and tight junction proteins in the colon tissues of the HIO (A) group were restored to levels similar to those observed in healthy mice. However, neither HIO (A) nor HIO (B) could be engrafted into the colon. Conclusions: Effective cell therapy should directly repair tissue by engraftment at the site of injury. However, the difference in organoid property impacting the rate of tissue repair in transplantation without engraftment observed in the current study should be considered a critical consideration in the development of regenerative medicine using iPS-derived organoids.

The Contribution of LIGHT (TNFSF14) to the Development of Systemic Sclerosis by Modulating IL-6 and T Helper Type 1 Chemokine Expression in Dermal Fibroblasts.

Systemic sclerosis (SSc) is an autoimmune and vascular disease resulting in multiple organ fibrosis, in which IL-6 and T helper (Th)2/Th17 cytokines serve as critical disease drivers. LIGHT is a proinflammatory cytokine promoting IL-6 production in lung fibroblasts and Th1 chemokine expression in dermal fibroblasts (DFs) stimulated with IFN-γ. In this study, we investigated the potential contribution of LIGHT to SSc development using clinical samples and animal models. In SSc-involved skin, LIGHT was upregulated in inflammatory cells, whereas herpesvirus entry mediator (HVEM), a receptor of LIGHT, was downregulated in DFs. Similar expression profiles of LIGHT and HVEM were reproduced in bleomycin-treated mice. Transcription factor FLI1 bound to the HVEM promoter, and FLI1 small interfering RNA suppressed HVEM expression in normal DFs. In SSc DFs, LIGHT significantly increased IL-6 production, whereas IFN-γ/LIGHT-dependent Th1 chemokine induction was decreased compared with that in normal DFs. Importantly, LIGHT small interfering RNA significantly attenuated bleomycin-induced skin fibrosis, and serum LIGHT levels were elevated in patients with diffuse cutaneous SSc and positively correlated with clinical parameters reflecting skin and pulmonary fibrosis. Taken together, these results suggest that altered response of DFs to LIGHT, namely increased IL-6 production and decreased Th1 chemokine expression, contributes to the development of skin fibrosis in SSc.

Endothelial CCR6 expression due to FLI1 deficiency contributes to vasculopathy associated with systemic sclerosis.

BACKGROUND: We have recently demonstrated that serum CCL20 levels positively correlate with mean pulmonary arterial pressure in patients with systemic sclerosis (SSc). Considering a proangiogenic effect of CCL20 on endothelial cells via CCR6, the CCL20/CCR6 axis may contribute to the development of SSc vasculopathy. Therefore, we explored this hypothesis using clinical samples, cultured cells, and murine SSc models. METHODS: The expression levels of CCL20 and CCR6 in the skin, mRNA levels of target genes, and the binding of transcription factor FLI1 to the target gene promoter were evaluated by immunostaining, quantitative reverse transcription PCR, and chromatin immunoprecipitation, respectively. Vascular permeability was evaluated by Evans blue dye injection in bleomycin-treated mice. Angiogenic activity of endothelial cells was assessed by in vitro angiogenesis assay. RESULTS: CCL20 expression was significantly elevated in dermal fibroblasts of patients with early diffuse cutaneous SSc, while CCR6 was significantly up-regulated in dermal small vessels of SSc patients irrespective of disease subtypes and disease duration. In human dermal microvascular endothelial cells, FLI1 siRNA induced the expression of CCR6, but not CCL20, and FLI1 bound to the CCR6 promoter. Importantly, vascular permeability, a representative SSc-like vascular feature of bleomycin-treated mice, was attenuated by Ccr6 siRNA treatment, and CCR6 siRNA suppressed the angiogenic activity of human dermal microvascular endothelial cells assayed by in vitro tube formation. CONCLUSIONS: The increased expression of endothelial CCR6 due to FLI1 deficiency may contribute to the development of SSc vasculopathy.

Serum levels of tissue factor pathway inhibitor: Potential association with Raynaud's phenomenon and telangiectasia in patients with systemic sclerosis.

Vasculopathy is a critical step of systemic sclerosis (SSc) development, bridging between autoimmune inflammation and tissue fibrosis. Impaired coagulation system is a part of SSc vasculopathy, but the role of tissue factor pathway inhibitor (TFPI), a critical regulator of the extrinsic coagulation pathway, remained unknown. Therefore, we evaluated the clinical correlation of serum TFPI levels in SSc patients. Serum TFPI levels were comparable between SSc and control participants, but SSc patients with Raynaud's phenomenon and telangiectasia had significantly lower serum TFPI levels than those without. Importantly, there was a significant positive correlation between serum TFPI levels and protein S activity. These results support the critical role of impaired coagulation system in SSc.

Association of serum CCL20 levels with pulmonary vascular involvement and primary biliary cholangitis in patients with systemic sclerosis.

AIM: Systemic sclerosis (SSc) is a chronic autoimmune disease resulting in vasculopathy and fibrosis of the skin and major internal organs. Especially, interstitial lung disease and pulmonary arterial hypertension are the leading causes of mortality. C-C motif ligand 20 (CCL20) is known as a homeostatic and inflammatory chemokine, which is associated with fibrosis and angiogenesis and constantly expressed in organs involved in SSc. Therefore, we investigated the potential contribution of CCL20 to the development of SSc. METHOD: We conducted cross-sectional analyses of 67 SSc patients and 20 healthy controls recruited in a single center for 9 years. Serum CCL20 levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed with the Mann-Whitney U test, the Kruskal-Wallis test followed by Dunn's multiple comparison test, Fisher's exact probability test and the Spearman's rank correlation coefficient. RESULTS: SSc patients had significantly higher serum CCL20 levels than healthy controls. In SSc patients, serum CCL20 levels correlated inversely with the percentage of predicated diffusion lung capacity for carbon monoxide and positively with mean pulmonary artery pressure (mPAP). In addition, SSc patients with increased serum CCL20 levels had anti-mitochondrial antibody M2 titer significantly elevated relative to those with normal levels, and SSc patients with asymptomatic primary biliary cholangitis (PBC) possessed higher serum CCL20 levels than those without. Importantly, serum CCL20 levels were associated positively with mPAP values and PBC presence by multivariate regression analysis. CONCLUSION: Serum CCL20 levels may be involved in the development of pulmonary vascular involvement leading to pulmonary arterial hypertension and asymptomatic PBC in SSc patients.

A potential contribution of decreased serum galectin-10 levels to systemic inflammation and pulmonary vascular involvement in systemic sclerosis.

OBJECTIVE: Galectin-10 (Gal-10) is a key molecule involved in eosinophil-mediated suppression of T-cell immune response. Systemic sclerosis (SSc) is characterized by T helper (Th) 2/Th17 immune response and impaired function of regulatory T cells, but the pathological role of Gal-10 has not been studied so far. Therefore, we investigated the clinical correlation of serum Gal-10 levels in SSc patients. METHODS: Serum Gal-10 levels were determined by enzyme-linked immunosorbent assay in 38 patients with diffuse cutaneous SSc (dcSSc), 30 with limited cutaneous SSc and 20 healthy controls. Clinical correlations of serum Gal-10 levels were examined. RESULTS: Serum Gal-10 levels were significantly lower in SSc patients than in healthy controls, especially in dcSSc patients, and inversely correlated with skin score, the percentage of predicted diffusion lung capacity for carbon monoxide and estimated right ventricular systolic pressure (RVSP). Furthermore, serum Gal-10 levels had negative correlations with leucocyte counts and inflammatory parameters. Multivariate regression analysis identified C-reactive protein and RVSP as explanatory parameters for serum Gal-10 levels. CONCLUSION: Decreased serum Gal-10 levels may reflect the impairment of eosinophil-mediated regulatory system for T-cell immune response in SSc, possibly contributing to pulmonary vascular involvement leading to pulmonary arterial hypertension.

Serum vasohibin-1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis.

Vasohibin-1 (VASH-1) is a potent anti-angiogenic factor mainly produced by endothelial cells. In addition, VASH-1 prevents TGF-ß-dependent activation of renal fibroblasts. Since systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs, VASH-1 may be involved in the development of this disease. In this study, we investigated the potential role of VASH-1 in SSc by evaluating the clinical correlation between serum VASH-1 levels and the expression of VASH-1 in SSc-involved skin. Serum VASH-1 levels were higher in SSc patients, especially those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, SSc patients with interstitial lung disease had significantly elevated levels of serum VASH-1 as compared to those without. Importantly, serum VASH-1 levels correlated inversely with both the percentage of predicted vital capacity and the percentage of predicted diffusion lung capacity for carbon monoxide and positively with serum KL-6 levels, but not serum surfactant protein D levels. In SSc-involved skin, VASH1 mRNA was remarkably upregulated compared with healthy control skin, but the major source of VASH-1 was not clear. Fli1 deficiency, a predisposing factor inducing SSc-like endothelial properties, did not affect VASH-1 expression in human dermal microvascular endothelial cells. Collectively, these results suggest that VASH-1 upregulation in the skin and sera is linked to dermal and pulmonary fibrotic changes in SSc, while the contribution of VASH-1 to SSc vasculopathy seems to be limited.

Serum S100A12 levels: Possible association with skin sclerosis and interstitial lung disease in systemic sclerosis.

Damage-associated molecular patterns (DAMPs) have drawn much attention as a member of disease-associated molecules in systemic sclerosis (SSc). In this study, we investigated the potential contribution of S100A12, a member of DAMPs, to the development of SSc by evaluating S100A12 expression in the lesional skin and the clinical correlation of serum S100A12 levels. S100A12 expression was markedly elevated in the epidermis of SSc-involved skin at protein levels and in the bulk skin at mRNA levels. The deficiency of transcription factor Fli1, a predisposing factor of SSc, enhanced S100A12 expression and Fli1 occupied the S100A12 promoter in normal human keratinocytes. Serum S100A12 levels were higher in SSc patients, especially in those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, the presence of interstitial lung disease significantly augmented serum levels of S100A12. Importantly, serum S100A12 levels correlated inversely with both per cent forced vital capacity and per cent diffusing capacity for carbon monoxide and positively with serum levels of KL-6 and surfactant protein-D. Collectively, these results indicate a possible contribution of S100A12 to skin sclerosis and interstitial lung disease associated with SSc, further supporting the critical roles of DAMPs in the pathogenesis of this disease.

Association of serum CXCL12 levels with arthropathy in patients with systemic sclerosis.

AIM: Systemic sclerosis (SSc) is an autoimmune connective tissue disease, in which extensive fibrotic change and vasculopathy affect the skin and various internal organs. It also involves the joints, causing stiffness, arthralgia, and arthritis. Although arthropathy is commonly observed in SSc, its underlying mechanism remains unknown. CXCL12, also known as stromal cell derived factor 1, is associated with inflammation, mesenchymal cell recruitment, angiogenesis, and collagen production, and is implicated in the development of various joint diseases. To assess the potential contribution of CXCL12 to SSc development, we investigated the clinical association of serum CXCL12 levels in patients with SSc. METHOD: We conducted a cross-sectional analysis of 68 patients with SSc and 20 healthy controls recruited in a single center over 9 years. Serum CXCL12 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum CXCL12 levels were significantly higher in patients with SSc than in healthy controls (median 1554.0 pg/mL, 25th-75th centiles 1313.0-1914.0 pg/mL vs 967.4 pg/mL, 608.8-1271.0 pg/mL, P < 0.001). Patients with SSc with elevated CXCL12 levels had significantly more cases of arthropathy than those with normal CXCL12 levels (85.7% vs 25.0%, P = 0.01). Furthermore, patients with SSc with elevated CXCL12 levels showed an increased trend in the prevalence of limited range of motion of the finger joints compared with those with normal CXCL12 levels (60.0% vs 18.6%, P =0 .07). Moreover, serum CXCL12 levels were significantly correlated with the titers of rheumatoid factor in patients with SSc (r = .41, P = 0.001). CONCLUSION: Elevated serum CXCL12 levels may be related to the development of SSc arthropathy.

Severe COVID-19 Pneumonia in a 30-Year-Old Woman in the 36th Week of Pregnancy Treated with Postpartum Extracorporeal Membrane Oxygenation.

BACKGROUND There are few reports of coronavirus disease 2019 (COVID-19) in pregnant women. Although coagulation dysfunction was reported to affect the severity of COVID-19, the association between pregnancy, which is usually accompanied by changes in coagulation function, and the worsening of COVID-19 is unknown. We present a case of a 30-year-old woman in the 36th week of pregnancy who was diagnosed with severe COVID-19 pneumonia and required postpartum extracorporeal membrane oxygenation (ECMO) therapy. CASE REPORT A 30-year-old, 36-weeks pregnant woman presented to our hospital and was diagnosed with severe COVID-19 pneumonia soon after she had undergone a cesarean section. Her respiratory failure could not be managed by conventional therapeutic approaches. Therefore, ECMO was administered on day 7. Controlling coagulation function to maintain ECMO therapy was challenging. Nafamostat mesylate and cryoprecipitate were administered to treat the hypercoagulative status and severe hypofibrinogenemia, respectively. Since coagulopathy and her respiratory state improved, the ECMO therapy was terminated on day 15. CONCLUSIONS We report a case of severe COVID-19 pneumonia in a pregnant woman urgently treated with ECMO in the postpartum period. Thus, this case highlights the importance of close monitoring and appropriate medical care for pregnant women with severe COVID-19 pneumonia.

Decreased serum cathepsin S levels in patients with systemic sclerosis-associated interstitial lung disease.

Cathepsin S (CTSS) is a lysosomal proteolytic enzyme regulating intracellular and extracellular biological activities, including immunity/inflammation and remodeling of vasculature and extracellular matrix, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSS in the development of SSc, we investigated the clinical correlation of serum CTSS levels. Because serum CTSS levels were inversely correlated with estimated glomerular filtration rate (eGFR) in SSc patients with renal dysfunction (eGFR, <60 min/mL per 1.73 m2 ), SSc patients with normal renal function (eGFR, ≥60 min/mL per 1.73 m2 ) were analyzed. Serum CTSS levels were significantly decreased in diffuse cutaneous SSc patients compared with limited cutaneous SSc patients and healthy controls. Among vascular and fibrotic clinical manifestations, Raynaud's phenomenon and interstitial lung disease (ILD) were relevant to a significant decrease in serum CTSS levels. Importantly, serum CTSS levels negatively correlated with serum levels of Krebs von den Lungen-6 and surfactant protein D in total SSc patients, while not correlating with modified Rodnan total skin thickness score and the percentage of predicted diffusion lung capacity for carbon monoxide and showing a positive trend with the percentage of predicted vital capacity. These results suggest a potential contribution of decreased CTSS expression to the development of ILD in patients with SSc.