A Case of a Highly Obese Covid-19 Patient with Severe Hypoxemia and Subcutaneous Mediastinal Emphysema Who Was Rescued by Early Introduction of ECMO.

We conducted the treatment of a highly obese patient with severe Covid-19 pneumonia who had a history of asthma. When she arrived at the hospital, she was already intubated and had mediastinal emphysema and severe hypoxemia. Because the patient's condition did not improve with mechanical ventilation, we introduced extracorporeal membrane oxygenation (ECMO) immediately after admission. The patient improved with early induction of ECMO and prone positioning. In the management of patients with severe Covid-19 pneumonia, early introduction of ECMO should be considered if oxygenation does not improve with mechanical ventilation, and prone positioning can also be effective.

CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis.

Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell-specific CD47-deficient (Cd47 ΔT) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47 ΔT mice required expression of its receptor signal regulatory protein α on cDCs. The development of CD4+ T helper cell-dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8+ T cells were both markedly impaired in Cd47 ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.

Surgical Repair Using Suture Bridge Technique for Triceps Tendon Avulsion.

Triceps tendon avulsion is a rarely occurring tendinous injury. Various surgical procedures, such as repair using sutures through the transosseous tunnel or suture anchors, have been reported for treating triceps tendon avulsion. However, standard surgical treatment has not yet been established. Here, we present a case of triceps tendon avulsion treated using the suture bridge technique. A 58-year-old man who fell on his left elbow from standing height presented to our hospital. Plain radiography revealed an avulsion fracture of the left olecranon process, suggesting triceps tendon avulsion. We performed surgical repair of the avulsed bone fragments and ruptured triceps tendon. We inserted suture anchors into the ulna, proximal to the fracture site, and passed the sutures through the full thickness of the triceps. Subsequently, fracture fragments were reduced and fixed by pulling them together with the triceps. We inserted knotless anchors into the ulna distal to the fracture site and fixed the avulsed bone fragments and triceps tendon using the suture bridge technique. The patient recovered well in five months and reported no elbow pain or limited range of motion. This suture bridge technique is advantageous as it prevents iatrogenic fracture and knot irritation, and it would be indicated in cases with poor bone quality or thin skin soft tissue of the olecranon.

Irreducible inferior shoulder dislocation requiring open reduction: A case report.

In inferior shoulder dislocation (ISD) cases, closed reduction usually achieves reduction and irreducible ISD is extremely rare. To date, only two cases requiring open reduction have been reported. Herein, we describe a case of an irreducible ISD that required open reduction. A 90-year-old woman fell at home and presented to our hospital. Plain radiography revealed a right ISD and greater tuberosity avulsion fracture. Because reduction under general anesthesia was difficult, we performed open reduction. The humeral head was entrapped by the inferior shoulder capsule. Since inferior instability remained after reduction, we reduced and fixed the greater tuberosity fracture and repaired the rotator cuff tear (RCT). This case suggested that humeral head entrapment by the inferior capsule and decreased force couple toward the humeral head by the greater tuberosity fracture and RCT cause irreducibility. Moreover, since instability can remain after reduction for ISD accompanying greater tuberosity fracture or RCT, preparing for implantations to repair these lesions is recommended.

SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis.

Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c+ cells of mice (SirpaΔDC mice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes of SirpaΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of SirpaΔDC mice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c+ cell-specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c+ cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self-reactive Th17 cells in the periphery as well as for the inflammation in the CNS.

SIRPα+ dendritic cells promote the development of fibroblastic reticular cells in murine peripheral lymph nodes.

Nonhematopoietic stromal cells contribute to the organization and homeostasis of secondary lymphoid organs by producing cytokines and chemokines. The development and maintenance of these stromal cells are thought to be regulated by innate immune cells. Indeed, we recently showed that signal regulatory protein α (SIRPα)-positive dendritic cells (DCs) are essential for the proliferation and survival of podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) in mouse spleen. We have now established an in vitro culture system for lymph node stromal cells (LNSCs) isolated from mouse peripheral LNs. Activated DCs and TNF-α each promoted the proliferation of cultured LNSCs, most of which were found to be Pdpn+ FRCs. Furthermore, ablation of SIRPα in CD11c+ cells attenuated this effect of DCs on LNSC proliferation. Transplantation of activated DCs together with cultured LNSCs into the renal subcapsular space markedly increased the number of ER-TR7+ stromal cells as well as induced the accumulation of T cells and increased the expression of Ccl19 in the transplants. Ablation of SIRPα in CD11c+ cells greatly impaired the development of LN-like structure in the transplants. Our findings thus suggest that SIRPα+ DCs are important for the proliferation and differentiation of Pdpn+ FRCs in peripheral LNs.

SIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen.

In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4+ cDCs as well as that of Pdpn+ FRCs and T cells in the adult mouse spleen. Such ablation also impaired the survival of FRCs as well as the production by CD4+ cDCs of tumor necrosis factor receptor (TNFR) ligands, including TNF-α, which was shown to promote the proliferation and survival of Pdpn+ FRCs. CD4+ cDCs thus regulate the steady-state homeostasis of FRCs in the adult spleen via the production of TNFR ligands, with the CD47-SIRPα interaction in cDCs likely being indispensable for such regulation.

Impact of Milrinone Administration in Adult Cardiac Surgery Patients: Updated Meta-Analysis.

OBJECTIVE: To determine the effects of milrinone on short-term mortality in cardiac surgery patients with focus on the presence or absence of heterogeneity of the effect. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Five hundred thirty-seven adult cardiac surgery patients from 12 RCTs. INTERVENTIONS: Milrinone administration. MEASUREMENTS AND MAIN RESULTS: The authors conducted a systematic Medline and Pubmed search to assess the effect of milrinone on short-term mortality in adult cardiac surgery patients. Subanalysis was performed according to the timing for commencement of milrinone administration and the type of comparators. The primary outcome was any short-term mortality. Overall analysis showed no difference in mortality rates in patients who received milrinone and patients who received comparators (odds ratio = 1.25, 95% CI 0.45-3.51, p = 0.67). In subanalysis for the timing to commence milrinone administration and the type of comparators, odds ratio for mortality varied from 0.19 (placebo as control drug, start of administration after cardiopulmonary bypass) to 2.58 (levosimendan as control drug, start of administration after cardiopulmonary bypass). CONCLUSIONS: Among RCTs to assess the effect of milrinone administration in adult cardiac surgery patients, there are wide variations of the odds ratios of administration of milrinone for short-term mortality according to the comparators and the timing of administration. This fact may suggest that a simple pooling meta-analysis is not applicable for assessing the risk and benefit of milrinone administration in an adult cardiac surgery cohort.

Effects of fibronectin on osteoinductive capability of fresh iliac bone marrow aspirate in posterolateral spinal fusion in rabbits.

STUDY DESIGN: A rabbit model of posterolateral intertransverse process spine arthrodesis was used. OBJECTIVE: To assess the osteogenic potential of hydroxyapatite (HA) sticks soaked with marrow and resultant strength in spinal fusion and effects of various biologic agents, in particular fibronectin (FN) on the strength. SUMMARY OF BACKGROUND DATA: Mesenchymal stem cells (MSCs) contained in marrow can differentiate into cells constituting bone, cartilage, muscles and fat. Unlike autogenous bone grafts, prosthetic bone grafts combined with marrow have failed to attain adequate strength of new bone even if they are used with marrow. METHODS: Porous HA sticks were used as a vehicle for new bone growth in spinal fusion. In experiment 1, rabbits received 2 HA sticks each with or without iliac marrow into the dorsal subcutaneous muscle. The sticks were explanted 6 weeks after surgery and tested mechanically and histologically. In experiment 2, 6 groups of animals underwent spinal fusions with 6 different bone grafts, either autogenous or prosthetic, and the local osteoinductive activity and mechanical strength of the fusion were evaluated. RESULTS: In experiment 1, the HA sticks implanted with marrow showed histologically more active osteogenesis and were mechanically stronger than those implanted alone. The increase in mechanical strength was significantly higher in the former group. In experiment 2, the spinal fusion with autogenous iliac bone was significantly stronger and more elastic than those with autogenous local bone and HA sticks with or without marrow (P < 0.05). The spinal fusion with HA sticks soaked with FN and marrow was significantly stronger than that with HA sticks soaked with marrow. The local osteogenesis after the fusion with HA sticks soaked with FN and marrow was more active than that with HA sticks plus marrow and HA stick plus FN. CONCLUSION: The impregnation of marrow into HA sticks produced histologically demonstrable active osteogenesis, possibly due to MSCs incorporated into the sticks. In the group receiving HA sticks soaked with FNand marrow, both osteogenesis and strength were increased to levels comparable to those achieved by spinal fusion with autogenous iliac bone grafts. It can be expected that the additional use of FN, which increases incorporation of MSCs into HA, will improve osteogenesis and hence the strength of the fusion.

Histological changes in intervertebral discs after smoking and cessation: experimental study using a rat passive smoking model.

BACKGROUND: Passive smoking has been reported to induce intervertebral disc degeneration in rats, and the objective of the present study was to histologically investigate changes in smoking-induced intervertebral disc degeneration after cessation of smoking. METHODS: Four-week-old rats were subjected to passive smoking for 8 weeks in a smoking box [20 cigarettes a day: one cigarette an hour (inhaled over 3 minutes and followed by ventilation with room air for 5 minutes)] to induce intervertebral disc degeneration. Smoke-free periods of different lengths were then established, and intervertebral discs were histologically analyzed. RESULTS: Immediately after 8 weeks of passive smoking, intervertebral discs exhibited cracks, tears, and misalignment of the annulus fibrosus, and increased fibrous tissue was seen in the nucleus pulposus. In addition, the level of interleukin-1beta in intervertebral discs was higher in the smoking group than in the non-smoking group. After cessation, progression of degeneration ceased, and the matrix of the nucleus pulposus and annulus fibrosus exhibited increased fibrous connective tissue and proteoglycan. However, there were no changes in annulus fibrosus misalignment. Interleukin-1beta levels also remained significantly elevated after 8 weeks of cessation. CONCLUSIONS: While the annulus fibrosus degeneration caused by smoking was partially irreversible after cessation of smoking, the amount of mucin (proteoglycan) in the nucleus pulposus and annulus fibrosus tended to increase after cessation, thus suggesting the possibility that smoking-induced intervertebral disc degeneration can be repaired to some degree by cessation of smoking.