Skin Infiltration Research Articles

Isolated erector spinae plane block (ESPB) for the anesthesia of axillary fossa: A case report

ESPB that has axial and sagittal spreads allows it to be as effective as the central blocks. Although its effectiveness on postoperative thorax analgesia has been vastly reported, the number of studies on its use in combination with other blocks for sedation purposes in the management of breast surgery anesthesia is limited. We present the anesthetic management of a patient for accessory breast tissue surgery by using ESPB block from T1. We observed that the effect of ESPB on skin incision and skin-related tissue retractions was limited while postoperative pain control was sufficiently managed by the skin infiltration with ESPB.

Dermatofibrosarcoma Protuberance of Male Breast: A Rare Case Presentation

We report a case of a 50-year-old man who is a chronic smoker, referred to our IBCC (Integrated Breast Care Centre) department, in AIIMS, Rishikesh with complaints of a lump in his left breast for 6 years. A 3×2 cm, ill-defined, firm to hard, non-mobile lump located in the upper and outer quadrant of the left breast which is beneath the previous surgical scar with skin infiltration is noted. Histological characteristics of DFSP are the arrangement of monomorphic spindle cells in a storiform pattern. It was staged as T4b N0 M0 and left wide local excisional biopsy of the tumor with a macroscopically free margin of 3 cm and sent for frozen section which revealed a dendritic differentiation with free margins and further confirmed on final histopathological examination. The postoperative recovery of the patient was uneventful. No loco-regional recurrence or distant metastasis was noted for 6 months of regular follow-up.

Clinical Characteristics, Immunophenotype and Outcomes of Blastic Plasmacytoid Dendritic Cell Neoplasms in a Peruvian Cohort

Background:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and fatal myeloid malignancy characterized by clonal proliferation of immature plasmacytoid dendritic cells. BDCN has been frequently described in men and age above 60 years, and usually involves the skin and bone marrow. Immunophenotyping is based on CD123+, CD4+ and CD56+ expression and is necessary rule out other myeloid malignancies. Objective: We aimed to describe the clinical characteristics and immunophenotype of BPDCN cases diagnosed at two tertiary Peruvian cancer institutions between 2018-2019. Methods: We retrospectively reviewed medical records of patients diagnosed of BPDCN at two tertiary Peruvian cancer centers (Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru) between 2008 and 2019. Clinical characteristics, treatments, outcomes and immunophenotype by pathology or flow cytometry review, were collected. Patients were classified according to their maturation stage using CD34 and CD117 expression into three subgroups: Immature-Intermediate blastic (IIB-BPDCN; partial expression of CD117 and absence or minimal expression of CD34), mature (M-BPDCN; absence of CD34 and CD117) and unknown(U-BPDCN). Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of immunophenotype. Results: Thirty-eight cases were included during the study period. The median age at diagnosis was 38 years (7-82), only six (16%) were older than 65 years, and a notorious female predominance (F/M ratio: 1.7:1) was observed. Twenty-four cases had CD34/117 expression available and were classified according to the maturation stage in IIB-BPDCN (13) and M-BPDCN(11), additionally 14 cases had unknown stage (U-BPDCN). Table 1 summarizes clinical characteristics, treatment and outcomes according to their immunophenotype. Bone marrow infiltration was more frequent in immature phenotypes (92% IIB-BPDCN vs 73% M-BPDCN, p=0.001), as well as skin infiltration was more common in mature phenotype (72% vs 31%, p=0.008). CNS infiltration at diagnosis was 15% and 55% in IIB-BPDCN and M-BPDCN, respectively. Sixteen patients received treatment based on ALL-like protocols, 8 AML-like, 5 CHOP-like and 9 patients only palliative care. At 5 years median follow-up, median EFS and OS was 12 and 16 months, respectively. IIB-BPDCN had the lowest survival (4 months EFS and 6 months OS). Conclusions: We describe a Peruvian cohort of BPDCN patients with younger age at diagnosis and female predominance than reported previously by other series, however further studies in Latino population are required to confirm these results. Immature phenotypes based on CD34 and CD117 expression were associated with high rate of bone marrow infiltration and fatal outcomes. New successful target therapies must be warranted for this rare and fatal condition. Disclosures No relevant conflicts of interest to declare.

Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Early detection of skin and cardiac amyloid deposits among asymptomatic carriers of hereditary pathogenic transthyretin mutation with normal electroneuromyography

Abstract Introduction During the last decade, disease modifying therapies have been proposed for hereditary amyloidogenic transthyretin (ATTRv) amyloidosis. It is essential to screen for disease onset among asymptomatic mutation carriers in order to trigger effective therapy as early as possible. We describe clinical and paraclinical data from ATTRv asymptomatic carriers, as a baseline assessment to detect disease onset and progression. Methods We retrospectively collected data of asymptomatic ATTRv carriers with normal electroneuromyography (ENMG), between March 1st 2015 and January 31st 2019, including: demographics, symptoms, physical exam, ENMG (initial and follow-up obtained in 73 patients, 56.2%), neurovegetative tests, skin biopsy (amyloid deposition, denervation), and cardiac evaluation (multimodal imaging, cardiac denervation and arrhythmias). Results We included 130 patients, aged 43.6 years (± 13.5), selected in family of a proband with an age of onset of 52.7 years (±15.7), 40.8% male, carrying 20 different variants of the TTR gene, including 63.8% Val30Met. Amyloid deposits on skin biopsy and/or cardiac fixation on bone scintigraphy, characteristic of amyloid infiltration, were found in 22/130 patients (16%). Skin biopsy was positive in 11 patients, and cardiac fixation on bone scintigraphy was positive in 15 patients. Amyloid infiltration was statistically associated with age (p=0.024), age difference from index case (p<0.001), electrophysiological carpal tunnel syndrome (p=0.022), interventricular septum thickness >12 mm (p<0.001), contrast enhancement in cardiac MRI (p=0.002), cardiac denervation using MIBG scintigraphy C/M ratio <1.85 (p=0.044). Multivariate analysis showed that age difference with index case and interventricular septum thickness were predictors for amyloid infiltration (OR=1.11, IC [1,04–1,19] and OR=1,76, IC [1,19–2,60]). Subgroup analysis showed electroneuromyography alteration during follow up in 11 patients (delay 26.9 months, range 10–49) with statistic association with amyloid deposits (55.6 versus 7.1% when ENMG was unchanged, p<0.001) and interventricular septum thickness (p<0.010). Conclusion Clinical and paraclinical assessment of asymptomatic carriers of ATTRv mutations shows that skin or cardiac amyloid infiltration may precede ENMG abnormalities in 16% of patients. This may trigger specific therapies in borderline cases. Age close to age of onset among index case and septum interventricular thickness appear as risk factors for developing electroneuromyogram alteration. Funding Acknowledgement Type of funding source: None

Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin-induced systemic sclerosis.

Mesenchymal stem cell (MSC) infusion has become a novel therapeutic strategy for complex autoimmune diseases; however, few detailed studies have been performed to investigate the benefit and mechanism of MSC treatment on systemic sclerosis (SSc). The present study aimed to evaluate the therapeutic effect of human umbilical cord derived-MSCs (UC-MSCs) on bleomycin-induced SSc in mice and explore the potential underlying mechanism. The murine SSc model was established by daily subcutaneous injection of bleomycin for 4 weeks, followed with two UC-MSC infusions every 7 days. Skin fibrosis was assessed by H&E and Masson staining. Flow cytometry was used to determine IL-17A, IFN-γ, tumor necrosis factor-β, IL-10 and IL-12 levels in serum samples and T cell subsets in murine spleen. Additionally, gene expression levels of cytokines and fibrosis markers in skin samples were measured by reverse transcription-quantitative PCR. Immunofluorescence staining was performed to track UC-MSC localization and lymphocyte cell infiltration in vivo. UC-MSC treatment exerted an anti-fibrotic role in bleomycin-induced SSc mice, as confirmed by histological improvement, decreased collagen synthesis, and reduced collagen-1α1, collagen-1α2, fibronectin-1 and α-smooth muscle actin gene expression levels. The results indicated that UC-MSC treatment only had a limited systematic effect on cytokine production in serum samples and T cell activation in the spleen. By contrast, T helper (Th)17 cell infiltration and activation in skin were efficiently inhibited after UC-MSC infusion, as evidenced by the decreased IL-17A and retinoic acid-related orphan receptor γt gene expression as well as IL-17A production. UC-MSC administration significantly ameliorated bleomycin-induced skin fibrosis and collagen formation primarily by eliminating local inflammation and Th17 cell activation in the skin; however, the systemic inhibitory effect of UM-MSCs on cytokines was less profound.

Using the Bolus in Post-mastectomy Radiation Therapy (PMRT): A National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group.

This study aimed to investigate the bolus practice among Italian radiation oncologists. In 2018, a survey on bolus application was sent to all members of the Italian Association of Radiotherapy and Clinical Oncology. The survey was joined by 102 radiation oncologists. Not all respondents answered to every question. A 69.5% of 82 respondents used bolus in case of skin infiltration and 52 of 68 respondents (76.5%) applied it every day. Skin was included as part of chest wall Clinical Target Volume both in the absence or the presence of breast reconstruction. Five mm bolus was the most used. 3D Conformal radiotherapy was the most used technique, in 73.5% of cases. Acute RTOG G2-G3 skin toxicity was recorded by 93.9% physicians. There was heterogeneity in the use of bolus, though an agreement was found in some topics. The achievement of a National Consensus may represent an interesting future goal.

Phosphatidylinositol-specific phospholipase C enhances epidermal penetration by Staphylococcus aureus

Staphylococcus aureus (S. aureus) commonly colonizes the human skin and nostrils. However, it is also associated with a wide variety of diseases. S. aureus is frequently isolated from the skin of patients with atopic dermatitis (AD), and is linked to increased disease severity. S. aureus impairs the skin barrier and triggers inflammation through the secretion of various virulence factors. S. aureus secretes phosphatidylinositol-specific phospholipase C (PI-PLC), which hydrolyses phosphatidylinositol and cleaves glycosylphosphatidylinositol-anchored proteins. However, the role of S. aureus PI-PLC in the pathogenesis of skin diseases, including AD, remains unclear. In this study, we sought to determine the role of S. aureus PI-PLC in the pathogenesis of skin diseases. PI-PLC was observed to enhance the invasion and persistence of S. aureus in keratinocytes. Besides, PI-PLC promoted the penetration of S. aureus through the epidermal barrier in a mouse model of AD and the human organotypic epidermal equivalent. Furthermore, the loss of PI-PLC attenuated epidermal hyperplasia and the infiltration of Gr-1+ cells and CD4+ cells induced by S. aureus infection in the mouse model of AD. Collectively, these results indicate that PI-PLC eases the entry of S. aureus into the dermis and aggravates acanthosis and immune cell infiltration in infected skin.

Daily Moxifloxacin, Clarithromycin, Minocycline, and Clofazimine in Nonresponsiveness Leprosy Cases to Recommended Treatment Regimen

Four patients (3 male; mean [SD] age at treatment, 41 [22.6] years) with nonresponsiveness lepromatous leprosy to regular MDT-MB were successfully treated with daily moxifloxacin, clarithromycin, minocycline and clofazimine for 24 months. There were reduction in the number and size of skin lesions and infiltrations, neural thickening (both visually and by palpation), bacteriological index, and leprosy reactions at 6 to 24 months after initiation of therapy.

A phase I, randomized, double‐blind study to assess the safety, tolerability and efficacy of the topical RORC2 inverse agonist PF‐06763809 in participants with mild‐to‐moderate plaque psoriasis

SummaryBackgroundTranscription factor retinoic acid‐related orphan receptor 2 (RORC2/RORγT) mediates interleukin (IL)‐17A and IL‐17F expression. IL‐17A plays a central role in the pathogenesis of several inflammatory disorders, including psoriasis. The RORC2 inhibitor PF‐06763809 has been hypothesized to inhibit IL‐17A production in T‐helper 17 (Th17) cells, thereby reducing psoriasis symptoms.AimTo assess the safety, tolerability and effect on skin infiltrate thickness of PF‐06763809 in participants with mild/moderate chronic plaque psoriasis.MethodsThis was a randomized, double‐blind, first‐in‐human study (trial registration: ClinicalTrials.gov NCT03469336). Participants received each of the following six treatments once daily for 18 days: three topical doses (2.3%, 0.8%, 0.23%) of PF‐06763809, a vehicle and two active comparators (betamethasone and calcipotriol). Primary endpoints included change from baseline in psoriatic skin infiltrate thickness [echo‐poor band (EPB) on ultrasonography] at Day 19, and safety. Change in psoriasis‐associated gene expression (Day 19), evaluated by real‐time reverse transcription PCR of skin biopsies, was an exploratory endpoint.ResultsIn total, 17 participants completed the study. Change from baseline in the EPB on Day 19 for all three doses of PF‐06763809 was not significantly different from that of vehicle (P > 0.05). A significant reduction in EPB from baseline was observed with betamethasone on Day 19 relative to all other treatments (P < 0.0001). Treatment‐related adverse events were mild/moderate. There were no significant differences in gene expression on Day 19 between vehicle and PF‐06763809‐treated skin lesions.ConclusionUsing a psoriasis plaque test design, PF‐06763809 was found to be well tolerated with an acceptable safety profile in participants with psoriasis, but without reduction in skin infiltrate thickness or disease biomarkers.

Emergent tracheostomy during the pandemic of COVID-19: Slovenian National Recommendations.

PurposeEmergent tracheostomy under local anaesthesia is a reliable method of airway management when orotracheal intubation is not possible. COVID-19 is spread through aerosol making the emergent tracheostomy a high-risk procedure for surgeons. The surgical establishment of the air conduit in emergency scenarios must be adjusted for safety reasons.MethodsTo establish the Slovenian National Guidelines for airway management in cannot intubate—cannot ventilate situations in COVID-19 positive patients.ResultsGood communication and coordination between surgeon and anaesthesiologist is absolutely necessary. Deep general anaesthesia, full muscle relaxation and adequate preoxygenation without intubation are initial steps. The surgical cricothyrotomy is performed quickly, the thin orotracheal tube is inserted, the cuff is inflated and ventilation begins. Following patient stabilisation, the conversion to the tracheostomy is undertaken with the following features: skin infiltration with vasoconstrictor, a vertical incision, avoidance of electrical devices in favour of classical manners of haemostasis, the advancement of the tube towards the carina, performing the tracheal window in complete apnoea following adequate oxygenation, the insertion of non-fenestrated canulla attached to a heat and moisture exchanger, the fixation of canulla with stitches and tapes, and the cricothyrotomy entrance closure. Appropriate safety equipment is equally important.ConclusionThe goal of the guidelines is to make the procedure safer for medical teams, without harming the patients. Further improvements of the guidelines will surely appear as COVID-19 is a new entity and there is not yet much experience in handling it.

Oxymatrine ameliorates imiquimod-induced psoriasis pruritus and inflammation through inhibiting heat shock protein 90 and heat shock protein 60 expression in keratinocytes

In this work, we aimed to investigate whether oxymatrine exerts its anti-pruritic and anti-inflammatory efficacy in the imiquimod-induced psoriasis mice and the related mechanism. We established the psoriasis model by applying the imiquimod ointment topically and oxymatrine was injected intraperitoneally as the treatment. The behavior and skin morphology results indicated that oxymatrine inhibits imiquimod-induced pruritus alleviating keratinization of skin and inflammatory infiltration. Moreover, we examined the expression of various indicators and found heat shock protein (HSP) 90 and 60 upregulated in model group, which were reversed in oxymatrine treated groups. Molecular docking and the studies in vivo confirmed that HSP90 and HSP60 participate in the inhibitory effect of oxymatrine on the phenotypes of psoriasis mice. Mechanically, immunofluorescence staining demonstrated that oxymatrine-induced downregulation of HSP90 and HSP60 was mainly in keratinocytes. In vitro results showed that oxymatrine decreases the expression of HSP90 and HSP60 upregulated by TNF-α and IFN-γ in HaCaTs cells and the siRNA mediated HSP90 and HSP60 silencing reverses inflammation inhibited by oxymatrine. Taken together, these results indicate that oxymatrine relieves psoriasis pruritic and inflammation by inhibiting the expression of HSP90 and HSP60 in keratinocytes through MAPK signaling pathway

Leukaemia cutis as a specific skin involvement in chronic myelomonocytic leukaemia and review of the literature: Acknowledgments.

The skin involvement of myeloid leukaemia is conventionally divided into specific malignant lesions and non-specific benign lesions, and these categories are also applicable in chronic myelomonocytic leukaemia (CMML). According to the 2016 World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues, CMML is defined as a myeloid neoplasm with characteristics of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs). As a specific cutaneous sign of extramedullary infiltration, leukaemia cutis (LC) is a rare occurrence in patients with CMML, and only approximately 89 cases have been reported in the literature thus far. The clinical features of LC are varied, and LC in CMML exhibits heterogeneous histopathologic features, with manifestations as cutaneous nodules or papules that are composed of blast cells showing either granulocytic or monocytic differentiation. Skin biopsy and further immunohistochemical examination are essential at the time of diagnosis to evaluate pathological type and determine the clinical course. Generally, once diagnosed as LC in CMML, this unusual skin lesion might be an indicator of transformation to acute myeloid leukaemia (AML) and is associated with a poor prognosis. The main treatment is allogeneic stem cell transplantation (ASCT). Therefore, early diagnosis and accurate identification have important therapeutic and prognostic significance in CMML patients with skin infiltration.

Abdominal extranodal lymphoma detection: positron emission tomography/computed tomography can help

BackgroundLymphoid neoplasms that present with masses are broadly referred to as lymphomas, and they can be classified to two main groups: Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL); they are mainly characterized by enlargement of lymph nodes (nodal disease) although any organ in the body can be involved in different settings of the disease (extranodal disease). Adequate staging, which has a direct impact on prognosis, is essential to properly plan therapy. Stage IV disease with extranodal dissemination should be treated by long-term systemic chemotherapy.By adding the metabolic changes to the conventional CT morphologic changes, combined positron emission tomography (PET) and computed tomography (CT) may offer clinically useful addition in staging of lymphomas and detection of extranodal lesions.ResultsThe study included thirty nine patients, with forty-eight extranodal sites with lymphomatous infiltration, twenty-four males (61.5%), and fifteen females (38.4%). The patients showed forty-eight extranodal abdominal lymphomatous infiltration.The study included twelve gastric lymphomatous lesions (25%), twelve splenic lymphomatous lesion (25%), three ileo-caecal lymphomatous lesions (6.25%), three patients (6.25%) with skin infiltration, three adrenal lymphomatous lesions (6.25%), three patients with hepatic lymphoma, and twelve bone marrow infiltrations (25%).The most accurate SUV max cutoff value among studied cases was 3.5, the highest SUV max value noted was 21 in gastric lesions, and the lowest SUV max noted was 4.1 in adrenal lesions.Confirmation of PET/CT results was done by histopathological assessment and post-management follow-up.ConclusionPET/CT study is an effective tool for evaluation of extranodal lymphomas. PET/CT fusion images can affect the clinical management plan by detection of extranodal lymphomas with lymphoma staging modification.

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas.

Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.

608 Targeting CtBP-mediated proinflammatory gene transcription to treat skin inflammation

Inflammatory skin diseases (ISDs) such as psoriasis and allergic contact dermatitis affects millions of people and poses a major public health burden. Aberrant cytokine production is a prominent characteristic of ISDs, although the molecular mechanisms underlying the imbalance between pro- and anti-inflammatory gene expression remain underexplored. C-terminal-binding protein (CtBP) 1 and 2 are transcriptional coregulators that repress diverse cellular processes. Our recently studies have uncovered a previously unrecognized proinflammatory role of CtBP in skin inflammation. CtBP1 overexpression in transgenic mouse keratinocytes causes a psoriasis-like phenotype including increased epidermal proliferation, immunocyte infiltration and proinflammatory cytokine expression in skin. Expression of the CtBPs is elevated in both human psoriatic skin lesions and the inflamed skin of two mouse ISD models, the imiquimod-induced psoriasis and the DNFB-induced contact hypersensitivity. Keratinocytes stimulated by imiquimod or DNFB exhibit transactivation of CtBP2 and CtBP-controlled proinflammatory genes that is accompanied by increased recruitment of CtBPs to the target promoters. Furthermore, we demonstrate that distinct CtBP-specific inhibitors can effectively suppress the expression of the CtBP target genes by evicting CtBPs from their target promoters and relieve symptoms of skin inflammation with topical treatment in both mouse ISD models. Together, these findings indicate that the CtBPs can promote skin inflammation by transactivating a select set of proinflammatory genes and suggest new avenues for therapeutic modulation of inflammation and immune responses in ISDs.

EFFECTS OF THE DIFFERENT ANESTHETIC METHODS ON POSTOPERATIVE HOSPITALIZATION AND USE OF ANALGESIA IN VARICOCELE SURGERY

Objective: The aim of this study was to evaluate the effect of different anesthetic methods used in varicocele surgery on postoperative pain relief needs and duration of hospitalization.Material and Methods: This study included 299 patients operated with varicocele between 2014 and 2018. patients were divided into general anesthesia+local anesthesia (20 ml prilocaine (2%)) skin infiltration [general anesthesia group (Group 1, n=50)], patients only administered spinal anesthesia [spinal anesthesia group (Group 2, n=142)], patients administered spinal anesthesia+TAP block [spinal+TAP block group (Group 3, n=52)] and patients administered spinal anesthesia and intrathecal morphine [spinal+ITM group (Group 4, n=55)].Results: The analgesic use in the general anesthesia group was not different from the spinal anesthesia group (p&amp;gt;0.05), but was different compared to the spinal+TAP group and spinal+ITM group (p&amp;lt;0.05, for both). Postoperative analgesic use is assessed for patients, the general anesthesia group was observed to have significantly shorter time for first analgesic use compared to the other groups (p=0.001). When patients are assessed in terms of the cost of anesthetic method, the highest cost method was in the spinal+TAP group. Conclusion: Despite relatively high cost of administration of spinal anesthesia+TAP block for varicocele surgery, it is an effective and reliable method with lower analgesic requirements and shorter duration of hospital stay.

Eliminating Opioids from Breast Conserving Surgery: Perioperative Pain Management Pathway

Opioid prescribing guidelines for partial mastectomy (PM) and PM with sentinel lymph node biopsy (PM-SLNB) recommend prescribing anywhere from 0 to 15 oxycodone pills for postoperative pain. We sought to eliminate opioids after breast-conserving surgery. In January 2017, we implemented a perioperative pathway in which patients received (1) preoperative acetaminophen, (2) pre-incisional bupivacaine skin infiltration, (3) post-excision bupivacaine wound deposition, (4) intraoperative ketorolac, (5) instructions to use both acetaminophen and ibuprofen for postoperative analgesia, and (6) counseling to set the expectation that opioids would not be required. We measured the percentage of patients who received, filled, and used opioid prescriptions. We compared this to historical institutional data from2016. There were 226 patients (mean age: 62 ± 13 years) who underwent surgery: 50% (114 of 226) underwent PM alone and 50% (112 of 226) PM-SLNB. Twenty-four patients (11%) required opioids in the recovery unit, and 14 (6%) were discharged home with a prescription. Five of the 14 patients (36%) did not fill their prescription. Among the patients who did fill their prescription, only 1 patient used opioids. In addition, 2 (1%) patients had difficulty managing their postoperative pain and were prescribed opioids within 7 days of surgery. Ultimately, 99% (223 of 226) of patients managed their postoperative pain after discharge without opioids. This represents a significant decrease in opioid use after breast conserving surgery, from 40% in 2016 to 1% after pathway implementation, p < 0.001. When a multimodal nonopioid pain pathway was implemented, 99% of patients undergoing breast-conserving surgery did not require opioids after discharge.

Inhibitory effect of Sihocheonggan‐tang on 2,4‐dinitrochlorobenzene‐induced atopic dermatitis in BALB/c mice

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation. Although the prevalence of AD has increased steadily in recent years, therapeutic treatments remain limited. In this study, we investigated the effects of Sihocheonggan‐tang (SHCG) on AD induced by 2,4‐dinitrochlorobenzene (DNCB) in BALB/c mice. Repeated application of DNCB was performed on the dorsal skin of BALB/c mice, and SHCG was orally administered daily for 2 weeks. We found that SHCG administration alleviated DNCB‐induced AD symptoms such as skin lesion and clinical skin severity score. Histopathological analysis indicated that SHCG significantly reduced the epithelial skin thickness and decreased the expression of thymic stromal lymphopoietin (TSLP), intercellular adhesion molecule‐1 (ICAM‐1), and mast cell infiltration in skin. Also, SHCG administration alleviated the increased immunoglobulin E (IgE) and Th2 cytokines such as IL‐4, TNF‐α, and IL‐6, induced by DNCB in BALB/c mice, suggesting that SHCG suppresses AD via the regulation of Th2 immune responses. Furthermore, we investigated the gut microbiota to clarify the association between AD and composition of gut microbiota. SHCG administration attenuated the abundance of Deferribacteres, which was increased in DNBC‐induced AD mice. Principal coordinate analysis (PCoA) revealed a separation of SHCG group from AD group at the species level. These results suggest that SHCG may be a promising therapeutic candidate for the treatment of AD by modulating gut microbiota composition.

Keratinocyte transglutaminase 2 promotes CCR6+ \u03b3\u03b4T-cell recruitment by upregulating CCL20 in psoriatic inflammation

Keratinocyte-derived cytokines and chemokines amplify psoriatic inflammation by recruiting IL-17-producing CCR6+ γδT-cells and neutrophils. The expression of these cytokines and chemokines mainly depends on NF-κB activity; however, the pathway that activates NF-κB in response to triggering factors is poorly defined. Here, we show that transglutaminase 2 (TG2), previously reported to elicit a TH17 response by increasing IL-6 expression in a mouse model of lung fibrosis, mediates the upregulation of cytokines and chemokines by activating NF-κB in imiquimod (IMQ)-treated keratinocytes. TG2-deficient mice exhibited reduced psoriatic inflammation in skin treated with IMQ but showed systemic immune responses similar to wild-type mice. Experiments in bone marrow (BM) chimeric mice revealed that TG2 is responsible for promoting psoriatic inflammation in non-BM-derived cells. In keratinocytes, IMQ treatment activated TG2, which in turn activated NF-κB signaling, leading to the upregulation of IL-6, CCL20, and CXCL8 and increased leukocyte migration, in vitro. Consequently, TG2-deficient mice showed markedly decreased CCR6+ γδT-cell and neutrophil infiltration in IMQ-treated skin. Moreover, TG2 levels were higher in psoriatic skin than in normal skin and correlated with IL-6, CXCL8, and CCL20 levels. Therefore, these results indicate that keratinocyte TG2 acts as a critical mediator in the amplification of psoriatic inflammation.