Due to the small number of cases and few literature reports, the clinical treatment and prognosis of lipid-rich carcinoma of the breast are not summarized, which will lead to misdiagnosis and mistreatment and delay the patient’s condition. This study collected published case reports and analyzed the clinical characteristics of lipid-rich carcinoma of the breast in order to provide reference for early diagnosis and treatment of the disease.We performed a search using the PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for publicly published case reports of lipid-rich carcinoma of the breast and obtained basic information of the patients such as country, age, sex, onset site, surgical method, pathology, postoperative treatment, follow-up time, and outcome Table . The datThe mean age of the patients at diagnosis was 52.79 years and the median age was 53 years. Breast masses were the main clinical manifestations, with the upper outer quadrant (53.42%) being the most common. The treatment for lipid-rich carcinoma of the breast is mainly surgery plus postoperative adjuvant radiotherapy and chemotherapy. According to the results of this study, the surgical method recommended modified radical mastectomy (46.59%). Lymph node metastasis was found in 50.60% of the patients at the time of the first diagnosis. Patients who received postoperative adjuvant chemotherapy and radiotherapy had the highest disease-free survival and overall survival.Lipid-rich carcinoma of the breast has a short course of disease and early lymphatic or blood metastasis, and its prognosis is poor. In this study, we summarize the clinical and pathological characteristics to provide ideas for the early diagnosis and treatment of lipid-rich carcinoma of the breast. Lipid-rich carcinoma of the breast (LRCB) is a very rare malignant tumor of the breast, accounting for 1–1.7% of all malignant breast tumors. LRCB is known to occur because tumor cells are rich lipids. Aboumrad was first discovered in 1963 . Later, LRCB is a rare special type of breast cancer, which has attracted the attention of clinicians because of its high malignancy, rapid progress, poor prognosis and lack of specificity in clinical manifestations. Due to the small number of cases of LRCB, there is not much summary of clinical treatment and prognosis of this disease at present. The management of LRCB remains controversial because it is prone to malignant transformation. Most authors advocate surgical treatment in advance when surgical treatment can be performed once the diagnosis is confirmed or neoadjuvant chemotherapy followed by surgical treatment followed by postoperative adjuvant treatment. The purpose of the current study was to collect sufficient patient queues to study the epidemiological, clinical, and pathological features of LRCB in order to better understand this rare disease.We performed a search using the PubMed, ClinicalTrials.gov, Embase, Cochrane Library, and CNKI databases from the date of their inception to November 30, 2021, without language restrictions, using the following search terms: “lipid-rich carcinoma of breast,” OR “lipid-secreting carcinoma of breast,” OR “lipid-rich breast cancer,” OR “lipid-secreting breast cancer”. All enrolled studies were confirmed based on the following criteria: (I) a clear diagnosis process is presented in the article, and (II) the third edition of the International Classification of Oncology Diseases (ICD-O-3.2) was used as a histological reference for diagnosis. The flow chart  country; (II) sex; (III) age at diagnosis; (IV) type of cancer; (V) whether the patients received chemotherapy and/or radiotherapy; (VI) whether and where the tumors metastasized; (VII) misdiagnoses (misdiagnosis criteria are obtained from the included literature); and (VIII) final results.This is a retrospective study, and all the data are from published and available database documents. This study was exempted from ethical approval procedures, because no clinical trials or randomized controlled trials were conducted, and individual consent was waived.The demographic, clinical, and pathological characteristics of the patients were described utilizing simple summary statistics; the categorical and continuous variables were analyzed using chi-square analysis and Student’s t-test.Statistical analyses were performed using the SPSS software , and one-sample K-S tests were used to determine whether the data conformed to a normal distribution. All tests were two-sided, and a p-value < 0.05 was considered statistically significant.This study included 68 articles Fig. , involviIn 91 samples detailing the tumor, the average tumor diameter was 3.63 ± 2.43 cm Table . By calcAll the patients included in the study were diagnosed with LRCB. According to the molecular classification standard of breast cancer, among the 46 patients who clearly provided the expression conditions of Her-2 and HR, Her-2(+) and HR (-) 17 cases (36.96%) were tri-negative breast cancer 11 cases (23.91%) were luminal A breast cancer 8 cases (17.39%) were luminal B breast cancer 10 cases (21.74%) Table . Among tOf the 88 patients who provided a detailed surgical protocol, 41(46.59%) underwent modified radical mastectomy, and 21(23.86%) underwent radical mastectomy. The choice of surgical approach was not only closely related to the patient’s condition but also to the era at that time. Of the 41 patients who received postoperative treatment, 22(53.66%) received chemotherapy + local radiotherapy postoperatively, 15 (34.15%) received chemotherapy only, 3(7.32%) received local radiotherapy only, 1(2.44%) received neoadjuvant chemotherapy, no chemotherapy was administered postoperatively, and 1(2.44%) received no postoperative treatment. However, among the 98 cases included, there were 69 cases (70.41%) in China and 78.57% in Asia  of the three patients who only received radiotherapy had distant metastasis. Three (20%) of the 15 patients who received chemotherapy and radiotherapy simultaneously had metastases. Of the 22 patients who received chemotherapy only, three (9.09%) had metastasis. Among the patients who clearly provided the pathological type and reported metastasis, Her-2(+) and HR (-) breast cancer patients had the most metastasis, accounting for 66.67%. This was followed by luminal B and tri-negative subtypes, accounting for 16.67% Table . HoweverRegarding the naming of LRCB, some researchers believe that lipid-secreting breast cancer is more appropriate. The appearance of lipids in breast cancer cells is the secretion product of the epithelial cells of the terminal duct, which is similar to the secretion activity of the mammary epithelium in the third trimester and lactation, but not steatosis. An ultrastructural study further confirmed this conjecture . Ramos  believedBreast mass was the main symptom at the onset of LRCB. Most patients complain of a breast mass. Few patients with metastases visited their doctors with the main complaint of tumor metastasis symptoms.LRCB is more common in unilateral breast masses, with or without pain. Color Doppler ultrasonography of the breast is the first choice for patients.The literature review shows that the age of onset of LRCB ranges from 10 to 83 years, and the peak age of onset is 40 to 55 years. Most LRCB patients are women, but men are even rarer. To date, only two male patients have been reported. The main clinical manifestation of LRCB is a breast mass, which can be involved in both breasts successively, most of which are unilateral. Occasionally, the right breast occupies space at the same time as the left breast, which is more common in the outer upper quadrant, followed by multi-quadrant occupying space. The diameter of the masses ranged from 0 cm to 12–3 cm, with 2–3 cm being the most common. LRCB usually has a short course of disease, usually within six months, and lymphatic or blood metastasis can occur in the early stage of LRCB. Lymph node metastasis occurs mostly in the axillary or supraclavicular region, and blood metastasis occurs mostly in the lung and liver. LRCB is characterized by high malignancy, rapid development, easy metastasis, and a poor prognosis.Because the number of lipid-containing cells needed to confirm the diagnosis of lipid-rich breast cancer is still unclear, the definition of a tumor remains unclear . HoweverThe differential diagnosis of LRCB includes primary and secondary vacuolar or clear-cell breast tumors as well as glycogen-rich carcinoma, apocrine carcinoma, and secretory carcinoma, all of which have different metabolites in the foamy cytoplasm . ① SecreTopoi-somerase II (Topo II) is a DNA topoisomerase encoded by Topo II, which has obvious cell cycle specificity. As a target of anthracyclines, related research has attracted increasing attention and has been used as a predictive marker in research and clinical practice. However, Topo II-α has not been widely detected in LRCB. Because it is adjacent to the Topo II-α gene, the probability of amplification of Topo II-α gene is 24.3% ~ 55% in primary breast cancer amplified by the HER2 gene . The ampP53 is one of the tumor suppressor genes with the highest correlation with human tumors discovered to date. The higher the expression of P53, the worse the differentiation of tumor tissues, the higher the malignancy, and the worse the prognosis. Among them, 50% of tumors have a P53 mutation . Mutant The expression of TOPO II in breast cancer can predict the biological behavior of breast cancer, especially anthracycline chemotherapy drugs, but the single index is insufficient for predicting the curative effect . Meta-anAt present, LRCB lacks unified treatment plan and standard, but we generally consider that once the diagnosis is confirmed, modified radical mastectomy or radical mastectomy with chemotherapy and/or radiotherapy should be performed. Because of the high rate of axillary lymph node metastasis in LRCB, axillary lymph node dissection is usually necessary. Lipid-rich cancers can metastasize immediately after surgery. The most common metastatic sites include the lungs, liver, and bones. Therefore, systemic therapy plays an important role in treatment. Lipid-rich cancers are usually positive for HER-2, but negative for hormone receptors, which is consistent with the results of this study. Because hormone receptors are negative, the effects of endocrine therapy are often limited. Therefore, chemotherapy is the most important component of LRCB. Compared with doxorubicin, lipid-rich carcinoma is more sensitive to platinum and molecular-targeted drugs (such as paclitaxel and vincristine) . In addiThe prognosis of LRCB is poor and there is currently no targeted treatment. Once the diagnosis is made, measures should be taken according to the principle of high-grade breast cancer treatment, and patients with surgical indications should undergo radical mastectomy. LRCB surgery often results in local recurrence. The first metastatic site is usually the axillary lymph node, which easily metastasizes to the orbital soft tissue. It can also metastasize to the contralateral breast, lung, liver, and bone along the blood channel, and half of these patients die within two years. Therefore, great importance should be attached to this disease. Although only a few cases of LRCB have been reported, the prognosis of this cancer is very poor. The overall 2-year and 5-year survival rates were 64.6% and 33.2%, respectively , and theIn summary, this study analyzed the clinical features, pathology, treatment, and prognosis of LRCB and emphasized that LRCB is a rare type of breast cancer. Owing to its poor prognosis, a correct diagnosis is necessary for this extremely rare tumor. Early diagnosis and timely treatment may help improve the overall survival and disease-free survival of patients with LRCB.


This case report aims to describe a case of GNET with challenging mesenchymal, lymphoid, and melanic tumor differential diagnosis. (2) Case presentation: We discuss the case of a 67-year-old male patient who presented with diffuse abdominal pain, intermittent lack of intestinal transit, and frequent episodes of nausea, followed by segmental resection of the jejunum and sigmoid colon. The patient had no relevant medical history. The surgical specimen underwent immunohistochemical staining and morphological evaluation. (3) Results: Histopathological analysis reveals a moderately homogeneous polyhedral-epithelioid and spindle cell neoplastic proliferation with a zonal discohesive pattern and extensive and focal fasciculated architecture. Twenty monoclonal antibodies were used for immunostaining, which allowed GNET to be diagnosed on the basis of the tumoral immune profile, characterized by positive reactivity of S100, SOX10, and CD 56. (4) Conclusions: The poor prognosis of GNET is highlighted in the present study, along with the vital importance of differential diagnosis issues with mesenchymal, lymphoid, and melanic tumors, which make the diagnosis difficult for both pathologists and clinicians. A malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare primary neoplasm with a distinctive histopathological, immunohistochemical, molecular, and ultramicroscopic profile, synonymous terminology with a clear cell sarcoma-like tumor of the gastrointestinal tract (CCS-like tumor of the GI tract) .Although it shares common molecular genetic abnormalities with the condition known as malignant gastrointestinal neuroectodermal tumor (GNET), clear cell sarcoma is a rare sarcoma that infrequently develops as a primary tumor in the gastrointestinal tract. However, it is distinguished from GNET by its morphological and immunohistochemical findings . Since tCurrently, a CCS-like tumor of the gastrointestinal tract  most likely represents a distinct entity from clear cell sarcoma (CCS) and is discussed in the 5th Edition of WHO Digestive system tumors volume. Many experts favor the name “CCS” when Melan-A, HMB45, or MITF are expressed and the term “malignant GNET” when these markers are not present ,2,3,4,5.In contrast to tumors described as gastrointestinal (GI) tract CCS, which have a higher median age  and a more significant percentage of male patients (85%), the incidence of tumors reported as GNET has a median patient age of 33 years (range: 10–81 years) and an even sex distribution [t chromosomal translocation and the emergence of the EWS-ATF1 fusion transcript [Rosai , statinganscript .EWSR1 gene rearrangement using molecular biology techniques and the absence of melanogenesis using ultrastructural data. To date, at this moment, 111 cases have thus far been documented in the literature [As the hypothesis progressed, Stockman et al.  establisterature ,11. GNETThis study will report a case of GNET with intestinal occlusion as a clinical symptom of the jejunal tumor’s colonic development. Mesenchymal, lymphoid, and melanic tumors present differential diagnosis challenges due to the neoplasm’s microscopic characteristics.These issues were solved by using immunohistochemistry, which is crucial for finalizing the diagnosis. Moreover, having as a starting point the presentation of this case, a literature review was carried out, oriented toward the clinical, cytogenetic, and electron microscopy traits of GNET.3 was noted. The computed tomography (CT) of the abdomen and pelvis revealed a large heterogeneous, hypoenhancing mass in the left flank near the jejunal loops, measuring 12 × 8.5 × 14.5 cm , and palliative; but unfortunately, the patient died. The surgical specimen consisting of a 25 cm small intestine and an 18 cm large intestine, which strongly adhere to each other, reveals in the jejunal segment a 13 cm-length ulcer-infiltrative lesion with circumferential growth. The section surface shows a white-grayish translucent aspect with transmural involvement and extension to the mesentery and sigmoid colon. The consistency is variable due to the alternate of the firm and friable areas. The enteral wall corresponding to the described lesion highlights a 5 × 4 cm continuity solution with gray-yellowish deposits. Pericolonic adipose tissue exhibits vascular thromboses associated with 0.5–0.8 cm whitish nodules. The surgical specimen was processed in the Pathology Department using standardized analytically validated protocols: fixation in 10% formalin, paraffin embedding, sectioning at 4-μm, and staining with hematoxylin and eosin (H E). Microscopically, a relatively discohesive pattern and massive and focal fasciculated architecture are observed A. The maAn immunohistochemical evaluation was performed using several monoclonal antibodies . The appThe tumoral immune profile  is charaBased on the morphology and tumoral immunoprofile, a diagnosis of malignant gastrointestinal neuroectodermal tumor (GNET) was made.Kandler T. et al. claim that although the median age at diagnosis ranges from 33 to 36 years ,11,12,13In other investigations by Chang B. et al., Zambrano E. et al., Stockman D.L. et al., and Damle A. et al., patients typically exhibit intestinal symptoms such as abdominal discomfort, distension, obstruction, ascites, pelvic effusions, or abdominal tumors, either clinically or on imaging ,10,12,13Contrarily, the Chang B. et al. analysis found that in 29% of instances, metastatic disease is frequently present at diagnosis . This vaTo date, there is still no agreement on the best systemic chemotherapy and targeted therapeutic alternatives for individuals who are not candidates for surgical excision because of significant metastases at initial presentation .The problem in this case report is that it is hard to tell GNET apart from other mesenchymal, lymphoid, and melanocytic tumors. When CCS-like tumor of the gastrointestinal tract manifests clinically or radiologically as masses in the gastric or intestinal wall that frequently cause intestinal obstruction, several differential diagnoses can be made, including adenocarcinoma, gastrointestinal stromal tumor (GIST), leiomyosarcoma, neuroendocrine tumors (including carcinoid tumors), and lymphoma .The absence of a melanoma clinical history helps rule out metastatic melanoma as a primary differential diagnosis, although conclusive evidence of an EWSR1 gene rearrangement is required . These sThrough their 16-case series, Stockman et al., who promoted treating GNET as a separate tumor entity rather than a variety of CCS, coined the term “GNET” in 2012 ; Table . Only 11Furthermore, due to its rarity and similarity to other tumors, GNET is frequently misdiagnosed and treated improperly.Primitive epithelioid, oval, or spindle tumor cells and sizable cells that mimic osteoclasts are typical features of this type of tumor. Because of the diverse histology, notably significant epithelioid or spindle cell components, these tumors might be mistaken for a range of other diagnoses, including a poorly differentiated carcinoma, such as a sarcomatoid carcinoma, according to a study by Chang B. et al. . The absence of melanin pigment in every instance reported distinguishes CCS-like tumor of the gastrointestinal tract from CCS and melanomas affecting the gastrointestinal system ,16,17,18Fascicles of largely uniform spindle cells morphologically represent the majority of most of GIST with minimal pleomorphism, occasionally having paranuclear vacuolations or palisading, and sometimes displaying epithelioid and pleomorphic variants as well as, very rarely, osteoclast-like large cells. Zambrano et al. highlighted that a CCS-like tumor of the gastrointestinal tract differs from CCSTA in that it may feature osteoclast-like giant cells (OLGC) and does not display the distinctive markers of melanocyte development .It is still debatable whether GI tract CCS and malignant gastrointestinal neuroectodermal tumors should be considered different tumors or the same tumor with varying degrees of differentiation ,2.A thorough IHC panel that includes cytokeratins, S100, and SOX-10 can also be used to identify the tumor as a GNET, and unlike carcinomas, GNET is cytokeratins negative .IHC features that identify GNET tumors include S100 and SOX-10 protein positivity and the absence of melanocytic-specific markers like HMB-45 and Melan-A.GNET frequently shows positive immunohistochemical results for S100 and SOX10 but negative results for markers more closely related to melanocytes, such as HMB45, Melan-A, and MITF. In any case, CD56 and SYN positive is a distinguishing trait of GNET diagnosis .Routine immunohistochemistry should make it easy to rule out CCS-like tumor of the gastrointestinal tract, devoid of the expression of DOG1, CD117, or CD34, which are expressed by more than 90% of GISTs. DOG1 and CD34 are expressed by the majority of GISTs with KIT negative ,23.In cases when Melan-A, HMB45, or MITF are expressed, many specialists prefer the word “CSS”, while in cases where these markers are absent, they prefer the term “malignant GNET” ,3,4,5,15The strategies incorporated by Stockman et al. that GNET tumors may arise from a primitive cell with a neural line of differentiation and no melanocytic characteristics that are connected to the autonomic nervous system ,16 also Stockman et al. have suggested that CCS-like tumor of the gastrointestinal tract be referred to as a “malignant gastrointestinal neuroectodermal tumor” due to the ultrastructural and immunohistochemical characteristics that support neural/neuroectodermal differentiation ,10.EWSR1 rearrangements were found in 12 of 14 cases (86%). The distinctive t and t chromosomal rearrangements of the GNET culminate in the production of the chimeric fusion proteins EWSR1-ATF1 and EWSR1-CREB1, respectively [EWSR1 rearrangements were present in 93.3% of the Chang et al. study cases, and both investigations used fluorescence in situ hybridization (FISH) to identify these rearrangements [A retrospective analysis by Stockman et al.  revealedectively . In contIt still needs to be determined if some GNET patients’ better clinical outcomes result from their slowly developing disease biology or from more aggressive treatments, such as recurrent aggressive surgical operations and systematic therapy regimens. The patient in this case study had a poor clinical course and a poorer prognosis following the surgical treatment. Otherwise, it is argued that GNET is a biologically diversified condition, equivalent to all other cancer forms, although relatively rare.To conclude, we consider that more research is required to develop standardized staging and therapy options for malignant GNET because there is currently no established procedure for its management.In this case report, we described a case of a 67-year-old male patient without significant history, presenting with the clinical appearance of intestinal occlusion, diagnosed with GNET based on the morphology and immunophenotype, with an unfavorable clinical outcome and a worse prognosis after surgical intervention. The current report highlights the importance of early diagnosis of GNET because of its variable prognosis and highlights the critical importance of differential diagnosis problems with mesenchymal, lymphoid, and melanic tumors, which make the diagnosis challenging for pathologists and clinicians alike.In conclusion, to help physicians design individualized treatment plans, it is critical to understand the biology of this disease.


Surgical treatment of finger nerve injury is common for hand trauma. However, there are various surgical options with different functional outcomes. The aims of this study are to compare the outcomes of various finger nerve surgeries and to identify factors associated with the postsurgical outcomes via a systematic review and meta-analysis.The literature related to digital nerve repairs were retrieved comprehensively by searching the online databases of PubMed from January 1, 1965, to August 31, 2021. Data extraction, assessment of bias risk and the quality evaluation were then performed. Meta-analysis was performed using the postoperative static 2-point discrimination (S2PD) value, moving 2-point discrimination (M2PD) value, and Semmes–Weinstein monofilament testing (SWMF) good rate, modified Highet classification of nerve recovery good rate. Statistical analysis was performed using the R (V.3.6.3) software. The random effects model was used for the analysis. A systematic review was also performed on the other influencing factors especially the type of injury and postoperative complications of digital nerve repair.Sixty-six studies with 2446 cases were included in this study. The polyglycolic acid conduit group has the best S2PD value (6.71 mm), while the neurorrhaphy group has the best M2PD value (4.91 mm). End-to-side coaptation has the highest modified Highet’s scoring (98%), and autologous nerve graft has the highest SWMF (91%). Age, the size of the gap, and the type of injury were factors that may affect recovery. The type of injury has an impact on the postoperative outcome of neurorrhaphy. Complications reported in the studies were mainly neuroma, cold sensitivity, paresthesia, postoperative infection, and pain.Our study demonstrated that the results of surgical treatment of digital nerve injury are generally satisfactory; however, no nerve repair method has absolute advantages. When choosing a surgical approach to repair finger nerve injury, we must comprehensively consider various factors, especially the gap size of the nerve defect, and postoperative complications.Type of study/level of evidence Therapeutic IV. Finger nerve laceration is one of the most common injuries in hand trauma, and its incidence rate is high in the peripheral nerve injuries of the upper limbs . Most haFinger nerve repair currently has two main surgical approaches. End-to-end tension-free neurorrhaphy has traditionally been the preferred repair method in lesions with a gap smaller than 5 mm . When thIn addition to the surgical method that may affect the functional outcomes, other predictors of sensory recovery have been evaluated in several studies, such as mechanism of injury gender, age, involved digit, level of injury, time from injury till repair, and gap length. The main one is the type of injury, which can affect the severity of the nerve damage, the gap between the nerve defects, and the recovery after surgery. According to Kusuhara et al. , avulsioFew systematic reviews and meta-analyses have been conducted to compare surgical approaches and factors associated with sensory outcomes of digital nerve repair. , 10–13 IWe performed and reported this review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.We performed systematic literature search in PubMed. The search terms “digital nerve,” “operation,” “surgery,” “nerve injury,” “nerve repair,” were combined using Boolean operators. Both “free-text term” and “MeSH term” searches were completed. We did not impose any restrictions on the language. The publication date was set from January 1, 1965, to August 31, 2021, because the clinical implementation of the surgical microscope started around 1965. The previous surgeries without microscopes were not included in the study . AdditioTwo authors screened the articles independently based on the titles and abstracts, and each author independently retrieved and examined the full texts of the relevant papers for inclusion/exclusion based on predefined stratified criteria. Finally, we included all prospective and retrospective studies on surgical treatment of finger nerve injuries, including observational cohort studies, randomized controlled trials, and case reports with detailed data. We included patients of all ages with finger nerve injuries. The data published on the included studies were analyzed for the outcomes. We included results with at least 6-month follow-up. Exclusion criteria were peripheral nerve lesions not localized to the digital nerves in the hand, duplicated data, without appropriate data analysis methods, inconsistent data, reviews, unpublished literature, conference papers, studies without adequate information. The PRISMA flowchart is shown in Fig. The primary author extracted data onto a predefined electronic data extraction form, and then, the other author checked all the data. Any disagreements were resolved through discussion, if necessary, with the involvement of a third reviewer. We extract the following data from each included literature, the characteristics of the literature , population characteristics , damage and repair status , complications .The outcome measurements we used included: static 2-point discrimination (S2PD), moving 2-point dis crimination (M2PD), Semmes–Weinstein monofilament testing (SWMF), and modified Highet classification of nerve recovery . Weber fWe used a modified classification system derived from Imai et al. to group SWMF outcomes. The SWMF scores ≤ 2.83 mean “normal” for sensation, scores from 2.83 to 4.31 mean “diminished light touch,” scores from 4.31 to 4.56 mean “diminished protective sensation,” scores from 4.56 to 6.10 mean “loss of protective sensation,” and scores > 6.10 mean “anesthetic” . We counMedical Research Council scoring system from 1954, modified by MacKinnon and Dellon often referred to as modified Highet, grouped a range of values into subjective headings . This scIn the S2PD and Highet data sets, there were many accounting articles, large amounts of data, and more detailed data. Therefore, we divided artificial catheters into two subgroups: collagen tubes and polyglycolic acid catheters. We divided venous catheters and muscle-in-vein grafts into groups in the autograft method. Direct suture and end-to-side anastomosis were split into two subgroups of neurorrhaphy for analysis. For these two data groups, we divided them into artificial conduit: polyglycolic acid, artificial conduit: collagen, nerve allograft, autograft repair: muscle-in-vein graft, autograft repair: vein graft, autologous nerve graft, end-to-end coaptation, end-to-side coaptation, total 8 repair types.There were fewer articles in the M2PD and SWMF data sets, so the data we extracted were limited. When summarizing and analyzing the data, we did not conduct a detailed subgroup analysis but merged them into five repair Types for analysis. They were: artificial conduit (collagen tubes/polyglycolic acid catheters), nerve allograft, autograft repair (muscle-in-vein graft/vein graft), autologous nerve graft, and neurorrhaphy (end-to-end coaptation/end-to-side coaptation).In addition, to evaluate the outcomes of the surgical repair methods, we also summarized and analyzed other factors associated with the result. These factors mainly included age, never gap, injury type, repair time, and smoking. Of course, the most important of these factors is the type of injury, which affects the degree of nerve damage, the choice of the surgical method, and postoperative recovery. We analyzed 25 articles , 16–38 wComplications reported in the studies were mainly neuroma, cold sensitivity, paresthesia, postoperative infection, and pain. We also conducted a summary analysis.2 test was used to assess the heterogeneity of the model. However, in order to reduce the difference between the parameters and avoid error of the results caused by heterogeneity, the random effects model was used to merge the statistics. For postoperative S2PD and M2PD of various surgical methods, we use a combined statistical analysis of mean and standard deviation. For the SWMF excellent rate and modified Highet score excellent rate, we adopted a combined statistical analysis of the rates. The results of the merger were displayed in a forest diagram, and the statistics were compared in the form of a table. We used funnel chart and egger test for publication bias. In the analysis by surgical method and injury type, the continuous variables of S2PD were compared by T test, and the excellent and good rates were compared using the chi-square test.Our meta-analysis was performed by R (V.3.6.3) and package of meta. Heterogeneity variance parameter IWe used standardized critical appraisal instruments from the JBI Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix II) to evaluate all included literature. Because all the included studies were case series or cohort studies, we used JBI Critical Appraisal Checklist for Descriptive/Case Series to evaluate the quality of the literature. This evaluation checklist includes 9 quality items, and the judging options include yes, no, unclear, and not applicable. Studies that blinded the evaluators and had “yes” scores of 80% were considered high quality; those with “yes” scores of 60–80% were rated as medium, and the quality of studies with a score of less than 60% was considered low. Any disagreements that arose between the reviewers were resolved through discussion.We searched the PubMed database using keywords and got 403 different publications. At the same time, we examined the reference lists of the included papers and previous reviews to add 45 records. Sixty-six articles were included in the final data analysis –76, 86 .The 66 articles included a total of 2446 cases. Fifty studies –76, 86 wP values derived from Egger’s test indicated their inexistence of the publication bias in most meta-analyses. The results of the Egger test are summarized in Tables All 66 articles were evaluated for the quality assessment using the JBI-MAStARI evaluation tool, and the research evaluation levels were high or medium. The specific evaluation results are shown in Tables All the data extracted from the literature are shown in Table A total of 51 articles reported the S2PD data , 76, 86.The excellent rate of modified Highet’s scoring includes 61 articles –76, 86. The M2PD group included 19 articles , 68, 69.There were 29 documents included in the SWMF data set , 76, 86.Finally, we conducted a summary analysis of all the data in the 4 outcome indicators. S2PD was 8.18 mm , M2PD was 5.90 mm , Highet score excellent and good rate was 80% , and SWMF excellent and good rate was 81%  Table , 12, 13.P > 0.05). In terms of the excellent and good rate, the recovery effect of sharp injury was better than that of blunt injury only in the surgical method of neurorrhaphy (P = 0.00004472), and there was no statistical difference in the other methods  were the worst. These 2 techniques have disadvantages for longer distances such as the collapse of the vein or dispersion of the regenerating axons out of the muscle . We founThrough a summary analysis of all the data in the 4 outcome measures, we found that most patients had a good recovery after nerve injury repair. According to the modified Highet classification of nerve recovery, both S2PD and M2PD achieved S3 + or better. The Highet score and SWMF excellent and good rate were all above 80% Table . We founThe surgical approach significantly impacts nerve injury and is a critical factor in surgical intervention. The mechanism of injury is another important factor that may affect the degree of damage, the length of nerve defect, the choice of the surgical method, and the outcome of postoperative recovery. Many scholars have researched this factor in the literature included in our study. Kusuhara et al.’s nine studies , 72, 74 There are other factors that may affect the postoperative recovery of neuroremediation. In the 5 studies included, it has been shown that age was a factor that affected nerve recovery, especially in children, whose recovery after nerve repair was better than that of adults and the elderly , 36, 74.Our analysis of the postoperative complications in the included literature found that neuroma, cold stimulation, paresthesia, and pain were the most reported after autograft surgeries. This may be due to the damage to the donor site and poor recovery of the recipient site after transplantation. For complications, the application of allogeneic nerves and nerve conduits was better than autograft.Our analysis has shown that the length of the nerve defect would affect the postoperative recovery, as well as limit the choice of surgical methods. Of course, we must also consider other factors, such as complications, economic conditions, local hospital technology, repair materials, etc. When there were multiple options to choose from for the optimal repair gap, we had to consider clinical factors associated with recovery when making the decision. There were no significant differences in the outcomes of various surgical methods, and the surgeon should choose a reasonable treatment plan based on the clinical scenario.There were several limitations of our study. First, the quality of our study is limited by the quality of the included studies, which were mostly case series (level 4 evidence). Second, the strength of our conclusions was limited by the heterogeneous and incomplete outcome data reported across the included studies, and publication bias for the individual studies analyzed. In addition, when analyzing the excellent rate of Highet score, not every study reported outcomes in the same manner. We were forced to use S2PD and M2PD classification systems to group the results into categories that were comparable across sensory outcomes.Our study demonstrated that the results of surgical treatment of digital nerve injury are generally satisfactory; however, no nerve repair method has absolute advantages. When choosing a surgical method to repair finger nerve injury, we must comprehensively consider various factors, especially the type of injury, the gap size of the nerve defect, the injury to the patient’s donor site, postoperative complications, the patient’s economic conditions, and the medical level of the local hospital. Whenever tension-free nerve coaptation was possible, end-to-end nerve coaptation was still the method of choice. In the case of nerve defects, the advantages of nerve conduits and allogeneic nerves were relatively high. When the proximal nerve was damaged and could not be connected, the end-to-side anastomosis technique could be selected for bridging to repair. Simultaneously, age, the size of the gap, and the type of injury were also factors that may affect recovery. Certainly, in consideration of the limitations of the study, such as the low qualities, the high heterogeneous, incomplete outcome data reported, and publication bias for the individual studies, conclusions in our study should be interpreted with caution. Therefore, more high-quality randomized controlled studies were definitely needed in order to give a conclusive statement.


This paper coupled a unified passive and active microwave observation operator—namely, an enhanced, physically-based, discrete emission-scattering model—with the community land model (CLM) in a data assimilation (DA) system. By implementing the system default local ensemble transform Kalman filter (LETKF) algorithm, the Soil Moisture Active and Passive (SMAP) brightness temperature  Soil moisture (SM) is a key variable in the Earth system linking the global water, energy and carbon cycles  and impaIn LSMs, the Richard equation with the specification of soil hydraulic properties   is used To obtain basic soil properties and associated SHPs at the large scale , the data assimilation (DA) strategy combining LSMs and observations has been investigated ,26,27. S to LSMs . Soil mo to LSMs ,29,30,31 to LSMs ,33. Whil to LSMs ,35,36,37 to LSMs ,39. Thes to LSMs ,40.Moreover, in SM retrieval, the current computation of the soil dielectric constant relies on semi-empirical formulations based on measurements over specific soil samples ,42. GeneDedicated studies have employed the zeroth-order RTM  to retrieve soil properties by assimilating TBp ,49,50. WTBp . This apin 2023)  and ESA in 2023) , it offein 2023) ,54. InclMany efforts have been made to develop the physically-based scattering-emission model through Maxwell’s equations under the support of the complementary relationship between the emission and scattering . The exaIn light of the above, the first objective of this paper is to include the aforementioned integrated ATS-AIEM-TVG (abbreviated as TVG) model with enhanced physical considerations as a unified passive and active microwave observation operator in a land DA system. This kind of physically-based microwave observation operator coupling is for the first time to the best of our knowledge. Specifically, the TVG is coupled with the CLM version 4.5   .The paper is organized as follows. The Maqu regional soil moisture and temperature (SMST) monitoring network ,66 is lodiometer  , saturated matric potential The Community Land Model (CLM)  is the ly et al.  PTFs wity et al. . In CLM y et al. ). Table y et al.  thermal y et al.  scheme, y et al. ,75. OtheIn this paper, the collected half-hourly atmospheric data involving wind speed, near-surface air temperature, near-surface relative humidity and air pressure, liquid precipitation, and incident solar and longwave radiation on the Maqu site  is takenThe TVG model ,76 assumIn TVG, the grass leaves on the Maqu site are described as dielectric thin discs, which exhibits a random orientation distribution . BistatiSoil surface scattering is computed by the AIEM  with thehis case ), which his case ). In thihis case , in whichis case ,81. The With the above computed scattering for vegetation and soil parts, respectively, the same matrix doubling algorithm is used to combine these two and obtain their interaction contributions. The scattering coefficients in the backward direction e L-band ,82,83, t Wilheit  coherentThe DasPy data assimilation system ,62 was dThe SMAP Level-1C ntervals  were extntervals . SMAP TBgiven in .https://www.bipm.org/en/committees/jc/jcgm/publications) (accessed on 23 February 2023). As described in In this study, the model physics, structure and parameterization involving the formulation of the PTFs described in  dataset  is selec dataset ,91; (2) reliable ; (3) thereliable ,93,94.The reference  run is driven by the in situ atmospheric forcing data over the period from 1 May 2016 to 30 October 2016 after the spin up to produce SMST profiles and land surface fluxes. The results of the Ref experiment are used to evaluate the accuracy of the DA experiments.https://rdrr.io/cran/geoR/man/grf.html, last accessed on 26 February 2023) of statistical data analysis software R is used to generate a Gaussian random noise field. The perturbed value is then the sum of the original values extracted from the SoilGrids1km dataset and the defined Gaussian noise field.To conduct the open loop and data assimilation experiments, both atmospheric forcing data and basic soil property data are perturbed, as uncertainties are assumed from these two sources, as previously mentioned. Specifically, the in situ atmospheric forcing data of precipitation, air temperature and radiation are perturbed, given their dominance in influencing SM, soil temperature and associated rding to  are listGiven the fact that the near-surface (~2.5 cm) soil contributes the most to soil emission in the L-band ,96, the Eventually, the 30 ensemble members with these perturbed atmospheric forcing data and soil parameters are obtained. An open loop (denoted as OL) experiment then is realized without implementing DA. It is noted that the selected ensemble size of 30 considers the effectiveness in balancing the ensemble performance and the cost of computational resources, as reported by ,97.The third and fourth experiments retrieve soil properties using the DA strategies over the soil-thawed period from 1 May 2016 to 31 August 2016. To identify whether the retrieved soil properties alone are sufficient to help improve estimates of land state variables  and land surface fluxes  by the CLM, the third experiment updates only soil properties, i.e., without updating SM (denoted as Only_Para). The fourth experiment (denoted as Joint_Updt) updates both the soil properties and soil moisture during the assimilation period, based on the state augmentation method  and a duIn the two DA experiments, the ensemble means of soil properties, rather than the perturbed property values for each member, are fed into the TVG model, as they are reported being more appropriate in parameter retrieval . MoreoveFinally, the retrieved soil properties obtained at the final assimilation step are compared to the in situ measurements with the root mean square errors (RMSEs) calculated. Therein, the clay fraction retrieved at high accuracy, to a great degree, is assumed in this study to reflect the success of soil property retrieval, given its outstanding roles in estimating SM and soil dielectric constant. That is, clay particles with platy-like structures contribute more to the overall specific surface of the soil for holding moisture than sand and silt particles with a smooth surface do . Moreove3) of the first layer obtained at the final assimilation step in the Only_Para and Joint_Updt experiments by assimilating SMAP The Joint_Updt experiment results show that the posterior distributions of both the retrieved sand fraction and clay fraction shift toward the truth b. The imThe two DA experiments with SMAP he truth . Althoughe truth , both DABased on the retrieved basic soil properties, the four soil hydraulic parameters are obtained through the Cosby PTFs. periment a, B decrshown in a. This ishown in b and botshown in  estimateand ψsat .In short, in the Only_Para experiment, the use of Furthermore, utilizing the prior depth ratio see , the pos3/m3 in 3/m3 in As eval see , the eva3/m3 vs. 0.08 m3/m3 in 3/m3 vs. 0.08 m3/m3 vs. 0.07 m3/m3 in After DA, the SM at 2.79 cm estimated in the Only_Para experiment is still higher than the in situ measurements, but exhibits slight improvements over the OL experiment  simulated in the reference experiment presents underestimations  is found to converge to 0.1 mriod see . For ins2 in 2 in this case) occurs to the reference estimated sensible heat flux (H), which is larger than the observations , with enhanced physical considerations is for the first time, to the best of our knowledge, coupled with CLM 4.5 in a data assimilation framework with the LETKF algorithm implemented. To investigate whether SMAP The results show the improvement of the soil property estimates by assimilating SMAP Comparing the assimilation results to the in situ observations indicates that the retrieved soil properties with a finer accuracy are not sensitive factors affecting the accuracy of the soil moisture estimates by the CLM. Uncertainties in the model structures relating to soil moisture estimates should be considered. For instance, optimizing PTF structures may be an alternative way to improve soil hydraulic property estimates and, thereby, soil moisture estimates, as more investigations ,109 indiLast but not least, DA is appreciated as tending to estimate the state of a large dynamical system based on limited information. DA applied to geoscience exhibits complexities, because it stands on its interdisciplinary nature across the observations of systems, dynamical systems, statistics and numerical optimization . Meanwhi


Significant concerns raise for the healthcare workers involved in airway management of patients diagnosed with coronavirus 2019 disease (COVID-19).Due to shortages of personal protective equipment (PPE), barrier enclosure systems such as aerosol box (AB) have been proposed worldwide. The aim of this study was to evaluate our experience using AB as protective equipment in patients with COVID-19 in a third-level center in Mexico.A retrospective study of COVID-19 patients requiring airway management using an AB in the Hospital Central Sur de Alta Especialidad de Pemex in Mexico City from March 1 to June 1, 2020. Antropometric data, pre-intubation vital signs, and laboratory tests were recorded; the primary endpoints were intubation success rate and complications associated with AB and patients’ mortality. As a secondary endpoint, AB subjective evaluation was explored by administering a survey after airway management procedures.Thirty-nine patients for a total of 40 intubations were documented. Thirty-one (77.5%) were men, with a mean age of 61.65 years; successful intubation occurred in 39 (97.55%) of the procedures, and AB was used in 36 (90%) of intubations, with success in 28 (70.0%); A Cormack-Lehane grade 3 view was recorded in 18 patients (46.2%), and during the procedure, the AB had to be removed in 8 (22.2%) cases, with migration documented in 91.6% of cases. The 30-day mortality was 48.71%, with 23.0% of patients discharged. 83.3% of surveyed anesthesiologists reported significant limitations in manipulating airway devices with AB used.Our data indicate that in clinical practice, the use of AB may hinder airway management and decrease the intubation success rate and may also result in patients’ injury. Further studies are necessary to validate the use of AB in clinical practice, and they should not replace certified PPE.The online version contains supplementary material available at 10.1186/s44158-022-00061-8. The recent severe acute respiratory syndrome due to the novel coronavirus 2 (SARS-CoV2) posed a series of challenges for any healthcare system globally, including the capability to handle critically ill patients’ surge, triage and ethics concerns, the need to redesign logistics, clinical pathways, and protocols, and the need to deal with healthcare workers’ (HCWs) risk of infection and need of personal protective equipment (PPE) .As of August 31, 2020, the impressive number of 25,721,294 confirmed cases and 856,289 deaths from coronavirus disease 19 (COVID-19) had been reported in the world, Mexico being the eighth country with the highest number of cases  and deaths , fifth in the American continent, after USA, Brazil, Peru, and Colombia [SARS-CoV-2 may infect the host by either large droplets and aerosol particles, therefore require airborne-level PPE for HCWs, particularly during aerosol-generating procedures (AGPs) , 4.As reported from other countries, HCWs have been affected by the COVID-19 infection, with around 12% of total infections in Italy , more thOther than correct social behavior and personal hygiene, specific protection policies for HCWs must include adequate PPE .The overwhelming nature of the COVID-19 pandemic, the worldwide unpreparedness, and conflicting information with regard to protection indications , 11 haveThis study was designed to assess the clinical performance and to report the clinical experience using an AB for airway management of COVID-19 patients in a tertiary-level medical center in Mexico.A retrospective review was performed, accessing data from an electronic database of patients diagnosed with COVID-19 and requiring airway management in the Central Sur Hospital of High Specialty of Pemex, Mexico City, from March 1 to June 1, 2020.3), and laboratory data  were collected before airway management.Accessing the database, only patient with confirmed COVID-19-positive polymerase chain reaction (PCR) test were enrolled for subsequent analysis. Demographic data was collected , past medical history , and drug addiction . Vital signs , arterial blood gas . Whenever possible, data for documented SARS-CoV-2 infection of HCWs involved in airway management was also retrieved.Primary endpoints of the study were intubation success rate, complications associated with AB, and patients’ mortality. As a secondary endpoint, the subjective evaluation of aerosol boxes was assessed with an ad hoc designed survey administered after airway management procedures to all anesthesiologists involved in the airway team any time the AB was used.Inclusion criteria were confirmed positivity for COVID-19 as from a positive PCR with a nasal swab in patients requiring airway management, using an AB.Exclusion criteria included lack of consent, patients intubated by other services besides anesthesia, missing data, and patients with known difficult airways.Written informed consent was obtained from all patients, relative, or caregivers upon hospital admittance, and the study received ethical committee approval by the ethics committee of the South-Central Hospital of High Specialty with number 51-20.Positive patient: a patient diagnosed with COVID-19 with a positive PCR;Successful laryngoscopy: intubation achieved on the first attempt;Failed laryngoscopy/intubation: inability to visualize laryngeal structures and/or to place the tube into the trachea;AB migration: movement of the AB from the original position during airway instrumentation ;The following definitions were used throughout the study:Operator discomfort for intubation: any limitation for natural movements because of the AB ports and/or perceived limitation for airway instrumentation.All intubations were performed by a two-anesthesiologists airway team, both of them senior anesthesiologists with residents only occasionally being included in the team and not with primary role. As suggested from different COVID-19 airway guidelines , 9, 13, The intubation device’s choice was left to the airway team leader, with two options for a standard Macintosh laryngoscope (with available blades sizes 3 and 4) or a King Vision video laryngoscope  with a size 3 blade. Adjuncts for laryngoscopy included malleable stylet or tracheal introducer.The AB used for airway management was a “first-generation” box consisting of a transparent acrylic cube, 50 cm 20 in) high x 50 cm (20 in) wide x 40 cm (16 in) deep, with two 10 cm (4 in) circular openings at 25 cm (10 in) from the base and 5 cm from the lateral face on the operator’s side , propofol (1–2 mg*kg-1), and rocuronium (1 mg*kg-1). Intubation attempted 60 s later. No manual ventilation was provided unless desaturation occurred and no cricoid pressure applied unless clear signs of regurgitation/aspiration.Airway evaluation was briefly performed before initiating the airway instrumentation procedure; this approach was maintained also in case of emergency intubations, taking account that expert anesthesiologists were always included in the airway team. Strategies to optimize peri-procedural oxygenation were undertaken during airway evaluation and patient’s preparation. The intubation procedure was performed after positioning the patient, and once the AB was placed above the patient’s head, with adhesive tape used to mark AB position and to secure it. A dedicated airway box was prompted close to the patient Fig.  and afteThe laryngoscope was introduced on the left orifice of the AB. The right orifice was used first for head manipulation, and the introduction of the endotracheal tube occluded with a Rochester clamp. After successful intubation, as confirmed by chest auscultation, peripheral saturation, and end-tidal carbon dioxide (when available), the operator’s arms were removed from the ports of the AB, the laryngoscope was placed in a bag for disinfection, the AB was removed after observation of original position landmarks, and the patient was transferred to the intensive care unit (ICU).In the event of an intubation failure, a second attempt was performed by the same or the second team member; after two failed attempts, or upon decision of the airway team leader, the AB was removed assuming it may cause interference, limitation, or potential harm.After use, the AB was cleaned and sanitized with a 10% sodium hypochlorite solution. After the procedure, the airway team members completed a nine items satisfaction survey for the AB use evaluating protection, comfort, problems with eventual migration, and the possibility for assistance by the second operator.A further question was also addressed, investigating any proposal of possible modifications and changes in the AB, and the final question was whether they would recommend its use. The survey was administered in electronic format and was entirely anonymous, and it was prepared ad hoc for the study given the lack of studies for in vivo clinical use of AB for COVID-19 patients airway management. The survey text is available in Additional file The results were evaluated using descriptive statistics for the non-parametric distribution: means, standard deviation and minimum-maximum intervals, and absolute and relative frequencies. The analysis was performed with the statistical package IBM SPSS Statistics 24.0 for Mac .A total of 40 intubations in 39 patients were performed (one patient was intubated twice). Thirty-one patients (77.5%) were men, with a mean age of 61.65. Patient information and comorbidities are listed in Table The most common symptom requiring intubation team activation and evaluation for intubation was dyspnea in 34 cases (85%), with a mean oxygen saturation before intubation of 79.8%.Overall, success with tracheal intubation was achieved in 39 (97.55%) of cases. The AB was used for 36 (90%) intubations. In the remaining 4 cases (10%), the AB use was excluded before the procedure because of the operator’s discomfort in 3 cases and because of the patient’s size in 1 case.In all cases, when the AB was used, the first attempt was successful in 28 cases (70.0%). In 8 patients (22.2%), it had to be removed because of failed intubation after multiple attempts with evidence of oropharyngeal injury . Given the paucity of available videolaryngoscopes in Mexico during pandemic and in lack of experience with their use, a standard Macintosh laryngoscope was used in all procedures, using a number 3 blade in 37 cases (94.9%) with an endotracheal tube 8 mm (20 cases), 7.5 mm (14 cases), and 7 mm (5 cases) inner diameter, and a tracheal introducer was used in 5 patients (12.8%).Mortality was followed-up at 30 days, with 19 fatalities (48.71%), 9 (23.0%) discharges, and 12 (30.76%) patients still in intensive care at the time of writing this paper.Twelve anesthesiologists performed the 40 procedures and completed the post-procedural survey.Ten anesthesiologists (83.33%) reported they felt safe using the AB, despite 11 (91.66%) reported a certain discomfort during the first uses of the AB. Eight (66.66%) claimed significant limitations in manipulating airway devices, with 10 (83.33%) reporting contact with the box walls. Migration of the AB was reported in 11 cases (91.66%), and in 10 patients (83.33%), help was required for the mobilization of the AB during the procedure.Between the proposed changes in the design of the AB, 11 anesthesiologists (91.66%) suggested to reduce height, 7 (58.33%) proposed a width reduction, and 4 (33.33%) larger ports. Overall, only 9 (75%) anesthesiologists would recommend AB for the intubation of COVID-19 patients.Among the anesthesiologists involved in the airway teams, 3 of them (25%) had documented SARS-CoV-2-positive nasal swabs at the end of the study.Our study shows that use of AB impedes airway management, with risks for patients in terms of intubation outcome and in terms of potential harm; as a further remark, the use of AB seems to superimpose infection risks for HCWs with evidence of increased cognitive and physical workload.COVID-19 represents an unprecedented challenge for healthcare system organization and facilities  with sigA recent review  suggestsOur data indicate that when the AB was used (90% of intubations), the first-pass intubation success rate was 70%. In 22.2% of cases, and the AB was removed because of multiple intubation attempts, with documented traumatic complications during airway management. This observation is in line with experimental studies and experts’ hypothesis as from relevant literature , supportThis finding may represent a bias, given that acquisition of line of sight with standard laryngoscope may be hindered by the optical and physical interface represented by the AB wall. Also, the need for intubation out of operatory room but in medical wards may have added difficulty to airway management, and this could be considered a biasing factor in AB evaluation.As a subjective data, 66.6% of physicians participating the study reported significant airway management limitations.Our study also raises concerns for patients and HCWs’ safety: the AB migrated during airway management in 91.66% of cases, which may have multiple implications: first, the box movement may complicate or compromise airway management attempts. Secondly, should the box move or fall from the bed, it may hit hurt the patient or the attending physician; last but not least, the box dislodgment may compromise the infection-control principle, if any.Interestingly, 83.3% of the providers reported physical contact with the box walls, with 33.3% suggesting the use of larger access ports. As reported in Begley’s simulation study , this coPerception of increased difficulty in airway management and risks for patients and HCWs was a common concern: In 10% of cases, the intubation team decided not to use the AB prior to the procedure either for comfort or patient’s size or perceived risk of difficult intubation during pre-procedural evaluation.The AB’s perceived protection was somewhat controversial: 83.3% of surveyed providers reported feeling safe with the device, whereas in 92% of cases some kind of discomfort was reported, and only 75% of participants recommended the use of barrier enclosure systems when filling the post-procedural report.Our study was underpowered to detect infection risks or incidence in HCWs, and it was not designed for such an endpoint. Nevertheless, at the end of the study, 25% of the intubation team members had a SARS-CoV-2-positive PCR nasal swab test, verisimilarly related to a clinical exposure.We may not exclude that an infection route was some aerosolization associated with the use of AB. As elegantly demonstrated in recent simulation studies, these devices may effectively stop the large droplets but they may not stop aerosols, with particles escaping through access ports via Bernoulli effect  or upon Concerns about safety and performance, and overall effects on airway management success, prompted the FDA to revoke the permit of AB in August 2020, so that barrier enclosures without the possibility of additional negative pressure are no longer recommended .Recent studies also highlight that any not fully enclosed AB may redirect aerosol toward the laryngoscopist, indicating that only an aerosol evacuation system may reduce aerosols inside the box, which should never substitute, but complementary to certified PPE , 33.Interestingly, recent evidence suggests that extubation may be even more critical in terms of aerosol generation and consequential infective risks ; the useWith 2.5% of all COVID-19-diagnosed Mexican patients requiring endotracheal intubation and invasive mechanical ventilation and a global 73.7% mortality , Mexico 46,013 (22.08%) of young (30––54 years old) Mexican HCWs developed a SARS-CoV-2 infection. The majority of them were not hospitalized, but between the 693 in critical condition, 234 required endotracheal intubation, with a case fatality rate of 1.48% (683/46 013) within HCWs compared with a global 15.26% , 39. A rPPE per se do not protect, unless users are not well trained in their use, in donning and doffing procedures and only if PPE are part of a wider strategy and preparedness , includiOur study has limitations as follows: first, it is a retrospective study conducted during the pandemic surge, and some data may have been missed or misreported. The survey responses were subjective, but we believe they may reflect quite objectively the clinical reality and HCWs feelings.We did not collect intubation duration data, nor could we carefully analyze data of HCWs infection rates, because of the study’s design, with a control arm missing.On the other hand, to our knowledge, this is one of the first clinical studies evaluating the use of AB in airway management in a series of 40 COVID-19 patients.Based on our experience, the use of barrier enclosure systems for HCW protection during COVID-19 airway management added complexity to airway instrumentation in our patients’ cohort. The use of AB did not seem to reduce the risk of HCW infection while increasing cognitive and physical loads, and the majority of our providers did not recommend the use of such devices. Proper use and adequate training in the use of PPE and development of training and organizational programs, including availability of medical equipment and social practices, should remain the primary options and gold standards for the protection of HCW’s during AGPs.Further studies are necessary before proposing the clinical use of AB and barrier enclosure systems.Additional file 1. Aerosol-box questionnaire in COVID-19 patients.


Curcumin, a natural polyphenol widely used as a spice, colorant and food additive, has been shown to have therapeutic effects against different disorders, mostly due to its anti-oxidant properties. Curcumin also reduces the efficiency of melanin synthesis and affects cell membranes. However, curcumin can act as a pro-oxidant when blue light is applied, since upon illumination it can generate singlet oxygen. Our review aims to describe this dual role of curcumin from a biophysical perspective, bearing in mind its concentration, bioavailability-enhancing modifications and membrane interactions, as well as environmental conditions such as light. In low concentrations and without irradiation, curcumin shows positive effects and can be recommended as a beneficial food supplement. On the other hand, when used in excess or irradiated, curcumin can be toxic. Therefore, numerous attempts have been undertaken to test curcumin as a potential photosensitizer in photodynamic therapy (PDT). At that point, we underline that curcumin-based PDT is limited to the treatment of superficial tumors or skin and oral infections due to the weak penetration of blue light. Additionally, we conclude that an increase in curcumin bioavailability through the using nanocarriers, and therefore its concentration, as well as its topical use if skin is exposed to light, may be dangerous. Curcuma longa [Curcumin is the main active ingredient in turmeric, obtained from the rhizome of ma longa ,2. This ma longa . Accordima longa ,5. The bma longa ,7,8. On ma longa ,11,12,13ma longa . The chema longa ,8. The lma longa . Curcumima longa . MembranThe effect of curcumin on membrane properties, as well as its location and orientation within the lipid bilayer, are under debate . On the Eucaryota is present exclusively in the inner mitochondrial membrane, where it constitutes about 20% of all lipids [One of the lipids which may prefer to interact with curcumin is cardiolipin. This lipid in l lipids . Becausel lipids ,30. Ben-l lipids  and contl lipids . In tumol lipids . Also, cl lipids ,35,36.max of about 420 nm). The process of reactive oxygen species generation by curcumin upon illumination, as well as curcumin’s role as a possible photosensitizer, will be discussed below. The other effects of curcumin on the structural properties of membranes may also have important consequences. The results presented by Duda et al.  suggest In model membranes, it has been shown that curcumin modulates the formation of lipid raft domains. Tsukamoto et al. observed that curcumin induces the fusion of lipid raft domains at extremely low concentrations through the alteration of the boundary between the ordered and disordered membrane phases . The autin vitro and in vivo in a rat model, curcumin was shown to have scavenging activity against free radicals such as superoxide radical anion (O2•−) and nitrite radicals. It was also effective at neutralizing hydrogen peroxide (H2O2) [The chemical structure of curcumin A determie (H2O2) ,41. Howee (H2O2) . Curcumie (H2O2) . It alsoe (H2O2) .Another important point in the consideration of the nonselective, systemic action of curcumin is its ability to up-regulate the expression of some genes, and in particular to enhance the production of enzymes involved in biological redox processes . On the other hand, curcumin may inhibit other enzymes, such as lipooxygenase and cyclooxygenase , and therefore prevent lipid peroxidation . There aIn addition to inhibiting lipid peroxidation, curcumin appears to reduce inducible nitric oxide (NO) synthase (iNOS) activity. This enzyme generates large amounts of NO, providing the “oxidative burst” necessary for the defense against pathogens in macrophages. This is possible due to the NO reaction with superoxide anion radicals to form peroxynitrite, which is highly toxic to cells . The eff1O2). Singlet oxygen, although not a free radical, is a highly reactive form of oxygen usually produced in photosensitized reactions, in which the excitation energy of a photosensitizer’s triplet state is transferred to molecular oxygen [1O2 photogeneration  and α-tocopherol, but not mannitol, which is considered a hydroxyl radical scavenger. Apart from scavenging free radicals and affecting enzyme activity, curcumin may also exert its antioxidant effect by quenching singlet oxygen (r oxygen . Das & Dr oxygen  studied adiation ). Das & radicals . Nonetheemission , suggestMelanin is the primary skin pigment synthesized by melanocytes, and to an even greater extent by melanoma cells, in a process called melanogenesis. Melanins, represented by eumelanin, pheomelanin and mixed melanin pigments, are the end products of the complex, multi-step transformations of L-phenylalanine and/or L-tyrosine, with or without L-cysteine and/or glutathione ,55. TheyThe regulation of melanin production via the melanocyte-specific melanocortin-1 receptor (MC1R) signaling pathway is a protective mechanism for the skin of living organisms against exposure to UVR .The stimulation of melanogenesis leads to a series of closely related oxidoreductive reactions, causing active melanogenesis, as well as causing melanin to consume oxygen, leading to relative intracellular hypoxia and a potentially mutagenic environment. In addition, the hypoxia-induced reprogramming of the metabolism from predominantly mitochondrial respiration to increased glycolysis in order to maintain ATP levels leads to HIF-1α activation, which, combined with immunosuppressive effects, leads to melanoma progression and resistance to immunotherapy. In addition, the biophysical properties of melanin make melanoma resistant to chemo- and radio-therapy . Therefo2O2 production [2O2 production in melanocytic cells [2O2 production affects melanogenesis [2O2, in the cells tested. In contrast, the addition of curcumin to the cells results in decreased H2O2 accumulation and melanin levels [2O2 and melanin levels appears to be dependent on H2O2 concentration. At H2O2 concentrations greater than 0.3 mM, the inhibitory effect of curcumin begins to prevail, so the effect of curcumin on melanogenesis in B16F10 cells will depend on their condition and how melanogenesis is stimulated [However, our study points to an additional mechanism of melanin regulation in melanoma cells treated with curcumin, which is the inhibition of Hoduction . Melanogic cells . On the ogenesis . Thus, mn levels . Interesimulated .Curcumin affects multiple signaling pathways that regulate survival, cell proliferation, apoptosis and tumor suppressor pathways . Based o1O2 and other ROS by curcumin in different solvents. Since then, the spectral and photochemical properties of curcumin in different solvents have been well described, which helps us to understand the biological photoreactivity of curcumin in various cellular microenvironments [in vivo.One of the first studies on curcumin behavior under illumination was of Chignel et al. , in whicronments ,71,72. Cronments ,10, ther2•−), and then in consequent reactions, hydrogen peroxide (H2O2), and eventually the powerful oxidant hydroxyl radical (HO•). The Type II process involves an energy transfer from the excited triplet state of a photosensitizer to molecular oxygen, which leads to the formation of 1O2. Interestingly, most photosensitizers used for PDT are believed to operate via the Type II rather than the Type I mechanism [Typically, photodynamic activity is related to Type I or Type II photosensitized reactions which lead to the formation of ROS . In Typeechanism . 1O2, superoxide radical anions and possibly H2O2 in the aprotic environment, and thus mediates oxygen-dependent phototoxicity in rat basophilic leukemia cells. Our recent studies have shown that curcumin under blue light irradiation (438 nm) can generate 1O2 not only in solvents, but also in liposomes, which were used as a model of cell membranes. In such systems, as well as in cells, the curcumin-generated 1O2 can diffuse into both the lipid and aqueous phases and cause the oxidation of the proteins and lipids present there. In particular, it was shown that curcumin-generated 1O2 was the main ROS responsible for the oxidation of cholesterol in liposomes and cells. The application of blue LED light (438 nm) in the presence of 10 µM of curcumin to HaCaT cells showed that the amount of 5α-OOH cholesterol hydroperoxides which are 1O2-specific [1O2 generation by curcumin was estimated to be about 4% [Dahl and co-authors  indicatespecific  was 5.5 specific . The quaabout 4% , which iabout 4% ), but se1O2) oxidize both lipids and membrane proteins [in vivo, limiting its potential use in PDT. The studies of Wozniak et al. [PDT is based on the use of light of a specific wavelength and non-toxic photosensitizers causing a photodynamic effect in order to treat various skin diseases or tumors. The dual-specificity of PDT relies on the accumulation of the photosensitizer in diseased tissue and also on localized light delivery . Due to proteins  Figure O2 oxidizproteins . Presumak et al.  on melank et al. . Therefo1O2, which can diffuse through a micro-organism’s cells and damage different structures. Curcumin-based PDT against micro-organisms makes sense, especially to combat drug-resistant biofilms, since their thickness ranges from 5 to 88 μm, through which even blue light penetrates. Curcumin-based PDT seems to be especially useful in the treatment of the bacteria and fungi responsible for oral and skin infections. In Streptococcus mutans in the presence of curcumin and Curcuma xanthorrhiza extract (CXE), and their mixture, decreases during 405 nm light-emitting diode (LED) irradiation, which can be used to prevent and treat tooth decay using devices that are readily available in clinics [Candida. Curcumin combined with LED irradiation was effective at inactivating biofilms and cell suspension cultures of clinical isolates of C. albicans, C. glabrata and C. tropicalis, promoting a reduction in the cellular metabolism by 85, 85 and 73%, respectively [C. albicans present in the tongues of mice with induced oral candidiasis, promoting an approximately 5log10 reduction in cell viability without causing any damage to the animals’ tongue tissues [C. albicans [Candida spp. infections is routinely based on the use of drugs, which can be topical or systemic [Staphylococcus aureus and Escherichia coli, and its antibacterial rates reached 93.04% and 92.82%, respectively. Interestingly, the antibacterial effectivity of the curcumin@Ag was better than that of the fiber membranes that were single-loaded with curcumin and Ag NPs. Additionally, the curcumin@Ag-loaded core/shell nanofiber membrane exerted a synergistic antibacterial effect on methicillin-resistant Staphylococcus aureus [The antimicrobial action of curcumin is widely described in a recent review . Here, w clinics . Oral ca clinics , can be ectively . The com tissues . Indepen tissues . Indeed,albicans . Widespralbicans . Treatmesystemic . Howeversystemic ,83 showesystemic . Besidesin vivo curcumin application for oral decontamination . Nine adults were treated with curcumin (30 mg/L) with an incubation time of 5 min and a blue light dose (200 J/cm2); nine adults were treated with only with the blue light (200 J/cm2); and nine adults were treated only with curcumin (30 mg/L). After the saliva samples were collected, the authors observed that the PDT group showed a significant reduction in microbial viability (up to 5.14 log10- post 1 h) compared with both the blue light and curcumin groups. Another example is the study on 45 adolescent patients performed by Paschoal et al. [in vivo evaluation of the antimicrobial and anti-inflammatory properties of curcumin under light activation on the plaque accumulation and gingival bleeding of adolescents under fixed orthodontic treatment. Patients were evaluated using curcumin (1.5 mg/mL) with a fluency of 96 J/cm2 and an incubation time of 30 min. After the photodynamic intervention, the dental plaque accumulation via the plaque index (PI) and the gingivitis condition via the gingival bleeding index (GBI), with 1 and 3 months of follow-up, were evaluated. The authors observed that curcumin under photodynamic action was able to control gingivitis after 1 month of follow-up. This outcome was explained by the photodynamic action as well as the anti-inflammatory properties of the curcumin photosensitizer. Although most of the studies have focused on bacteria and fungi cultures or biofilms, there are also examples of curcumin-based PDT in humans. Leite et al.  reportedl et al. . The autThe skin consists of the epidermis, dermis and subcutaneous tissue, serving as a self-regulating protective organ against environmental influences such as UVR. The body’s homeostasis is regulated by the local neuroendocrine and immune systems through a number of signaling molecules produced by resident and immune cells. The skin’s neuroimmunoendocrine system includes the epidermal neuroendocrine system and interactions with the central systems and organs. Epidermal cells are not only sensitive to neurohormonal regulation, but also produce elements of the hypothalamic–pituitary–adrenal (HPA) or hypothalamic–pituitary–thyroid (HPT) axis, other neuropeptides, biogenic amines, serotonin, melatonin, nitric oxide, opioids, cannabinoids, catecholamines, acetylcholine, steroids, secosteroids, neurotrophins and cytokines. The neuroimmunoendocrine system of the skin can activate central responses with direct homeostatic, metabolic and phenotypic consequences, as described in depth in . The con2O2 accumulation in cells, and the use of curcumin in this case showed its antioxidant effect. Moreover, curcumin has a weaker ability to generate H2O2 than 1O2 [1O2-induced oxidative stress leads to a decrease in mitochondrial membrane potential, an increase in membrane permeability and the release of cytochrome c. This activates caspase 9 and Apaf-1. Both caspase 8 and caspase 9 lead to the activation of caspase 3 and caspase 7, resulting in cell apoptosis  [Although the main point of criticism towards curcumin-based PDT is the low penetration of blue light, the studies mentioned in idermis) ; therefoin vitro experiments, and few on animal models, clinical studies are needed to prove its efficacy in PDT. Doing so, it has to be remembered that the therapeutic effect of PDT is determined not only by the bioavailability of curcumin, which can be significantly increased by using different carriers, but also by the depth of penetration of blue light into tissues. Although blue light is a high energy carrier, its ability to penetrate tissues is limited to a maximum depth of 0.3–2 mm [To the best of our knowledge, there are no clinical data available involving curcumin-based PDT against cancer. Because most of the current research on curcumin in combination with light is focused on 0.3–2 mm ,77. The 0.3–2 mm ,71. 1O2 by a single species, is a known phenomenon. For example, it was shown for melanin [In this review, we tried to emphasize the double role of curcumin as an anti- and pro-oxidant. From a biophysical point of view, one can be concerned that a compound which can both quench and generate singlet oxygen is neither a perfect photosensitizer nor a good protector against ROS. This would, however, depend on the environmental conditions. In the case of irradiating with blue light, curcumin can act as a photosensitizer, although its photodynamic effects are reduced by its simultaneous ROS quenching. The yield of singlet oxygen generation, which was shown to be at about 4%, is therefore an effective one, since without the quenching it could be higher. The antioxidant action of curcumin may prevail when samples are irradiated in the presence of another photosensitizer, such as Rose Bengal or porphyrins, which absorb light of longer wavelengths. Such a swap from anti- to pro-oxidant features, as well as the simultaneous generation and quenching of  melanin  and caro melanin ,130,131. melanin ,77. It s melanin  should nin vivo, and the lack of any convincing information on in vivo efficacy, as most of the current research literature includes only in vitro examples.As we tried to show in our review, curcumin, due to its natural origin, ease of acquisition and widespread consumption, has been studied thoroughly and in different aspects. Epidemiological observations indicate, for example, that the regular consumption of turmeric by the Asian population may promote a decrease in the incidence of various types of cancer in this population. Curcumin’s spectrum of action is very broad, which makes its usage tempting not only in traditional Chinese medicine but also in modern therapies. Curcumin has a relatively poor bioavailability, which, at first glance, may be a disadvantage. Hence, attempts are made to increase its bioavailability by using different carriers such as liposomes, nanoparticles, etc. However, it can be suggested that this poor bioavailability is the key to curcumin’s health-promoting effects, because, as mentioned above, an excessive concentration in cells or excessive exposure to UVor blue light can have the opposite, even undesirable, effects on healthy tissues. The use of high concentrations of curcumin makes sense only in anti-cancer or anti-microbial therapies such as PDT, when selectivity can be achieved by using nanocarriers or applying light that reaches only the affected areas. However, one has to underline, once again, that curcumin’s efficacy as a photosensitizing agent has serious limitations due to its inadequate absorbance spectrum, its application only to very small tumor volumes


Azospirillum brasilense has promisingly increased plant yield and nutrient acquisition. The study aimed to estimate the dose of A. brasilense that increases yield, gas exchange, nutrition, and foliar nitrate reduction. The research was carried out in a greenhouse at Ilha Solteira, in a hydroponic system in randomized blocks with four replicates. The treatments consisted of doses of inoculation with A. brasilense strains AbV5 and AbV6 via nutrient solution . Inoculation with A. brasilense at calculated doses between 20 and 44 mL provided the highest fresh and dry mass of shoots and roots, number of leaves, and leaf yield. In addition, the calculated doses of inoculation with A. brasilense increased the accumulation of N, P, K, Ca, Mg, S, B, Fe, Mn, and Zn in shoots and roots, except the accumulation of Ca in roots. It also increased cell membrane integrity index (15%), relative water content (13%), net photosynthesis rate (85%), intracellular CO2 concentration (15%), total chlorophyll (46%), stomatal conductance (56%), transpiration (15%), and water use efficiency (59%). Hence, inoculation with A. brasilense at doses between 20 and 44 mL 100 L−1 is considered the best approach for increasing the growth, yield, accumulation of nutrients, and gas exchange of hydroponically grown iceberg lettuce.Inoculation with  Lettuce is the most produced and consumed leafy vegetable in the world due to its desirable culinary characteristics for fresh consumption as salads . IcebergAzospirillum brasilense has been associated with several mechanisms, such as increasing the production of phytohormones, siderophores, and secondary compounds as well as performing biological nitrogen fixation and promoting nutrient use efficiency, which promote plant growth  × 100. Ten leaf discs 25 mm in diameter were collected at 8:00 a.m. (at dawn) from four leaves of each plant and then immediately weighed to obtain the fresh weight (FW). To obtain the turgid weight (TW), leaf discs were submerged for 12 h in distilled water at 25 °C; after that, they were gently dried on a paper towel and weighed. The samples were then oven-dried at 75 °C for 24 h and weighed to determine the dry weight (DW). The leaf membrane stability index (MII) was measured by Lutts et al.  at harveA. brasilense were adjusted by regression analysis at the 5% probability using SigmaPlot 15 software [As the data of all variables presented a normal distribution and homogeneous variances (Shapiro–Wilk Test), they were subjected to analysis of variance. The F-test was used to assess the significance of the mean squares in the analysis of variance at the 5% probability level. The means relative to inoculant doses with software .−1 of the inoculant of A. brasilense provided the highest yield of fresh leaves; that is, this is the dose indicated to achieve the greatest yield efficiency.The dose of 44 mL 100 LA. brasilense between 20 and 33 mL 100 L−1 improves the yield components and the accumulation of N, P, K, Ca, Mg, S, B, Fe, Mn, and Zn. Also, it was effective to perform biofortification with micronutrients in the leaves of iceberg lettuce plants in the hydroponic system.The use of doses of −1 of the inoculant with A. brasilense provided a better water status and gas exchange for lettuce plants, increasing photosynthetic, water use, and carbon assimilation efficiency.Doses between 20 and 33 mL 100 LA. brasilense strains AbV5 and AbV6 interacting with other factors, such as reduction or increase in the electrical conductivity of the nutrient solution, reduction in the use of fertilizers, management of N in the nutrient solution, and increased precocity for harvesting and other plant species.Based on the results obtained, further research should be carried out to explore inoculation via nutrient solution with