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Analgesia for Awake Internal Jugular Vein Cannulation in Trauma Emergency Bay: A Randomized Comparison of Ultrasound-Guided Superficial Cervical Plexus Block With Local Infiltration.

BACKGROUND: Internal jugular vein (IJV) cannulation is a critical component of trauma resuscitation but is often associated with significant pain during vessel dilation and suturing when performed under local anesthetic (LA) infiltration. OBJECTIVES: We hypothesized that an ultrasound (USG)-guided superficial cervical plexus block (SCPB) would provide superior analgesia and improve procedural efficiency in awake trauma patients compared to standard LA infiltration. METHODS: This was a prospective, randomized study of conscious, adult trauma patients requiring IJV cannulation. Participants were randomized to receive either 10 mL of 1% lignocaine via ultrasound-guided SCPB (Group S) or LA infiltration (Group L). The primary outcome was procedural pain measured by Numeric Rating Scale (NRS 0-10) during skin puncture, vessel dilation, catheter insertion, and suturing. Secondary outcomes included total procedure time, Verbal Numeric Rating Discomfort Scale (0-10), and complications. RESULTS: We enrolled 60 patients, with 30 patients assigned to each study group. Median NRS pain scores were significantly lower in Group S compared to Group L at all procedural time points (p < 0.01). The total procedure time was reduced by approximately 50% in Group S (7.5 min [interquartile range (IQR) 6.0-9.3]) compared to Group L (15.5 min [IQR 9.5-16.5]; p < 0.01). Patient discomfort scores were also significantly lower in Group S (p < 0.01). No periprocedural complications were reported in either group. CONCLUSION: Ultrasound-guided SCPB may be a useful alternative to local infiltration for IJV cannulation in selected awake trauma patients, when performed by clinicians experienced in ultrasound-guided regional anesthesia. By providing comprehensive sensory coverage, the technique significantly reduces procedural time and enhances patient cooperation without need for systemic sedation.

Humans

The spectrum of eosinophilic infiltration of the gastrointestinal tract and its relationship to other disorders of angiitis and granulomatosis.

Six cases of eosinophilic infiltration of the gastrointestinal tract were studied. Three cases were of the diffuse infiltrative variety (eosinophilic enteritis, two cases; eosinophilic peritonitis, one case), and three cases were of the circumscribed variety (so-called inflammatory fibroid polyp). Two of the infiltrative lesions showed necrotizing granulomas identical to those described by Churg and Strauss; one of the two also showed active vasculitis. One circumscribed lesion occurred in a patient with polyarteritis nodosa. Necrotizing eosinophilic granulomas were also noted in this lesion. Our observations suggest that the two forms of eosinophilic infiltration of the gastrointestinal tract are parts of a disease spectrum. Supporting evidence in the literature is presented. The relationship of this group of eosinophilic lesions to the hypereosinophilic syndrome, allergic granulomatosis and angiitis of Churg and Strauss, and polyarteritis nodosa is discussed.

Adult

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15&#x200a;years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24&#x200a;h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24&#x200a;h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6&#x200a;ml&#x200a;kg -1 of levobupivacaine 2.5&#x200a;mg&#x200a;ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg&#x200a;kg -1 in the TAP and infiltration groups, respectively ( P &#x200a;=&#x200a;0.95). FLACC scale values did not significantly differ between the two groups ( P &#x200a;=&#x200a;0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test&#x200a;=&#x200a;0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans

Predominance of T lymphocytes in the dermal infiltrate of atopic dermatitis.

Tissue sections from diseased skin of sixteen patients with atopic dermatitis were investigated with haematoxylin-eosin and toluidine-blue staining, with direct immunofluorescence staining using FITC-conjugated antisera against IgG F(ab')2 and IgM, and with the indirect immunofluorescence method utilizing specific rabbit anti-human T lymphocyte antiserum with FITC-conjugated goat anti-rabbit Ig antiserum as the second layer. Furthermore, cryostat sections were investigated in a closed chamber immune adherence method using aminoethylisothiouronium bromide (AET) treated sheep red blood cells to detect E receptors on T lymphocytes, and with various types of coated sheep red blood cells to detect cells with IgG Fc receptors and complement factor C3b receptors. All sections presented dermal perivascular infiltrates of mononuclear cells as judged by haematoxylin-eosin staining. Staining with toluidine-blue demonstrated varying numbers of mast-cells, but in no case pathological increased number. The majority of the infiltrating cells presented rim-like membrane fluorescence with the anti-T antiserum, and the AET treated sheep red blood cells (SRBC) adhered to the infiltrates, thus indicating a predominance of T lymphocytes in the skin infiltrates of atopic dermatitis.

Adolescent

Infiltrating neoplasms of the kidney.

Some neoplastic processes which involve the kidney develop not as a distinct localized mass, but rather as an infiltrating process which replaces the renal parenchyma, causes little or no mass effect, and contains little if any neovascularity. These neoplasms include (1) carcinoma of the renal pelvis when it invades the parenchyma (transitional cell and squamous cell); (2) blood-borne metastatic squamous cell carcinoma to the kidney (most frequently from the lung): (3) renal lymphoma of the infiltrating variety; and (4) infiltrating sarcomatous type of hypernephroma. While the urographic and angiographic appearance of these infiltrating lesions can be similar, clinical aspects are usually sufficient to differentiate them. Radiographic findings include amputation of portions of the collecting system on urography and encasement of vessels with a loss of nephrogram on angiography.

Adenocarcinoma

Sponge matrix allografts. A model for analysis of killer cells infiltrating mouse allografts.

A method for isolation of allograft-infiltrating cells in a functionally viable state is described in this article. The method is based on the use of a spongious tissue into which cells of strain A (e.g., fibroblasts or tumor cells) are grown. The resulting graft is then transplanted to a strain B animal, and the infiltrating cells are released from it by gentle compression. The graft-infiltrating cells are completely recovered, and they may be processed for further experimentation and analysis by employing exclusively physical methods of cell preparation. As an example of future applications, some preliminary results on density- and charge fractionation of the graft-infiltrating cells are also reported.

Animals

[Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications].

A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate.

Culicidae

The cellular infiltrate and its measurement in contact dermatitis.

It is well known that in the fully developed allergic contac reaction a marked cellular infiltrate takes place in the upper corium and epidermis. In the first part of this paper a short survey is given about the different cells taking part in the infiltrate and the efforts to differentiate both mononuclear and polymorphonuclear cells. In the second part is an account of our quantitative cell studies in experimental contact allergy in guinea pigs. Variations in the increase of mononuclear cell infiltration in epidermis or in the upper dermis seem to reflect the degree of hypersensitivity. Similarly a highly significant polymorphonuclear cell increase is seen in the allergic contact reaction compared to normal control skin, and basophils seem to predominate. The influence of cyclophosphamide methotrexate and corticosteroids on the cellular infiltrate of allergic contact reactions during its development has been studied.

Adrenal Cortex Hormones

The role of cellular locomotion in leukemic infiltration. An organ culture study on penetration of L 5222 rat leukemia cells into the chick embryo mesonephros.

The significance of cellular locomotion for leukemic infiltration was investigated using L 5222 rat leukemia cells. Previous cinemicrographic studies have shown that these cells are able to locomote only after formation of a uropod-like posterior extension. This characteristic locomotive configuration of L 5222 cells is easily recognizable in scanning electron micrographs and appropriate sections. Leukemia cells were inoculated on slices of chick embryo mesonephros incubated for 24h; at this time the fragments are completely encapsulated. Leukemic infiltration is found to begin within the first 2 h and to increase gradually up to the end of the observation period at 72 h. Spread of leukemia cells occurs mainly in the intertubular spaces; the tubular epithelium is only rarely affected. In all stages of infiltration, L5222 cells with the characteristic locomotive configuration are frequently recorded. Besides this strong although indirect indication for the significance of locomotion, further evidence was provided by experiments performed at 25 degrees C and 18 degrees C. In accordance with the previous cinemicrographic finding that at these temperatures L 5222 cells are unable to produce their posterior extension, no leukemic infiltration mesonephros fragments is recognizable at subnormal temperatures.

Animals

Benign and malignant proliferative response. Dermal infiltration, origin and importance.

Lymphoreticular infiltration (LRI) is the most common type of dermal infiltration. The LRI is made up of two main components: (i) a dermal skeleton, and (ii) the infiltration in a strict sense. (i) The dermal skeleton consists of the blood vessel involved, most probably a post-capillary venule, and activated fibroblasts (Fig. 3). The activated fibroblasts contain "paraplasmatic granules" in their processes (Fig. 4). Since the fibroblasts are in mutual contact by their ramifications (Fig. 3), they are reticulum cells by definition (Bessis). In our opinion they are the only local reticulum cells in the dermis. They are not stem cells, nor do they belong to the reticulo-endothelial system and they do not give rise to histiocytes. (ii) In the skeleton of LRI, other cells infiltrate, predominantly monocytes and lymphocytes. The LRI may specialize and contain various amounts of neutrophilic, basophilic, or eosinophilic leukocytes and plasma cells. If enough B-lymphocytes and plasmacells are involved, abnormal globulins may be produced (e.g. syphilis II). The lymphomas are considered to be malignant proliferative disorders of LRI-type. LRI is found in allergic spreading reactions mediated by stimulated lymphocytes. A similar spreading of lymphocytes is to be expected if the allergen sensitizes a lymphocyte with neoplastic information (e.g. tumor virus) (Fig. 6). The degree of dedifferentiation and the response of the organism to the dedifferentiated lymphocytes is the reason for the variety of lymphomas.

Basophils

MYH16 upregulation is associated with lung adenocarcinoma aggressiveness and immune infiltration.

Myosin heavy chain 16 (MYH16) may significantly affect cell cycle progression. Nevertheless, there is a lack of evidence about the clinical relevance of MYH16 upregulation in pan cancers, including lung adenocarcinoma (LUAD). MYH16 expression patterns were evaluated in various bioinformatics databases using The Cancer Genome Atlas data set. Clinical and pathological factor data were employed to risk-stratify patients. The Kaplan-Meier plotter approach was used to estimate survival rates. Tumor immune infiltration was explored via the TIMER tool, and gene set enrichment analysis (GSEA) was used to identify the pathways involved in MYH16 upregulation. The results showed that MYH16 was abnormally upregulated in pan cancers, including LUAD. MYH16 expression induction in LUAD was found to be related to the tumor stage. Furthermore, MYH16 upregulation was correlated with LUAD development and worse overall survival, particularly in women. Notably, MYH16 overexpression in LUAD tissues corresponded to the amount of immune infiltration in the tumor. Additionally, univariate Cox hazard regression analysis revealed that MYH16 may be an independent prognostic indicator for LUAD. Furthermore, a nomogram was constructed according to MYH16 expression and clinical characteristics. BMP6 expression deficiency may be a key factor contributing to MYH16 upregulation in LUAD. Finally, GSEA demonstrated that MYH16 might mediate meiosis and gene silencing through RNA signaling pathways. This study, for the first time, showed that MYH16 upregulation in LUAD is associated with various risk factors, increased cancer aggressiveness, enhanced infiltration of tumor immune cells, and reduced survival rates.

Female

Discovery of novel diagnostic biomarkers of hepatocellular carcinoma associated with immune infiltration.

OBJECTIVE: Diagnosis of hepatocellular carcinoma (HCC) remains challenging for clinicians. Machine learning approaches and big data analyses are viable strategies for identifying HCC diagnostic markers. MATERIALS AND METHODS: In this study, we downloaded mRNA expression profiles of HCC from the GEO database and used random forest and machine learning algorithms, such as least absolute shrinkage and selection operator, to screen for reliable diagnostic genes. Disease Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis enrichment analyses were performed to explore differential gene functions and disease pathways. CIBERSORT was performed to calculate the immune cell infiltration of HCC and the correlation between diagnostic genes and immune cells. Cell experiments were performed to evaluate the function of R-spondin 3 (RSPO3) in HCC cells. Immunohistochemical staining was used to evaluate the protein expression of CD138, CD206 and iNOS. RESULTS: The results indicated that extracellular matrix protein 1 (ECM1), Niemann-Pick C1-Like 1 (NPC1L1) and RSPO3 were down-regulated in HCC compared with the normal group (p&#x2009;<&#x2009;0.05), which was validated in clinical tissue samples. Moreover, ECM1, NPC1L1 and RSPO3 had high diagnostic values (AUC > 0.75) for HCC in both training and test groups. Immuno-infiltration analysis revealed that ECM1 and RSPO3 were highly positively correlated with neutrophil and macrophage M2 levels, whereas they were negatively correlated with Tregs. RSPO3-si affected cell proliferation and apoptosis in HCC. Furthermore, RSPO3 exhibited a positive correlation with tumour progression, the proportion of plasma cells and M2 macrophages in mice, while showing a negative association with M1 macrophages. CONCLUSION: The present study identified ECM1, NPC1L1 and RSPO3 as new diagnostic biomarkers for HCC based on normal and diseased samples from HCC, meanwhile the pro-oncogenic function of RSPO3 and its regulation on immune infiltration have been confirmed.

Carcinoma, Hepatocellular

Distribution of adenosine triphosphatase in infiltrating ductal carcinoma and non-neoplastic breast.

The histochemical reaction for adenosine triphosphatase (ATPase) has previously been used to differentiate myoepithelial from epithelial cells in the breast and to investigate the possible contribution of myoepithelial cells to mammary carcinoma. Discrepancies in published reports prompted this study of ATPase in non-neoplastic breast and infiltrating ductal carcinoma. ATPase was localized mainly on myoepithelial cells of normal breast and was identified with significant frequency on epithelial cells in hyperplastic ducts. Infiltrating ductal carcinomas usually displayed a variable reactivity. In one instance, malignant cells demonstrating mucin production were found to be ATPase-positive. An infiltrating ductal carcinoma of the papillary type with apocrine features was also strongly ATPase-reactive. It is concluded that ATPase is not an exclusive marker of myoepithelial cells and, therefore, data resulting from the use of this enzyme to study the role of the myoepithelium in mammary carcinoma must be interpreted with caution.

Adenosine Triphosphatases

The significance of perivascular infiltrations in multiple sclerosis.

143 autopsy cases of multiple sclerosis (19 acute and 124 chronic cases) were analysed histologically for the extent of active demyelination and the degree of infiltration within and outside the demyelinating lesions and in the leptomeninges. The results were compared with the duration of the illness. Infiltrations were found in 60% of all cases but more often (74%) in those with active demyelination. Inflammatory lesions outside demyelinating foci were observed in 27% of the total, and in 80% of them active demyelination was present. Inflammatory lesions in the meninges were present in 41% of the total and in 80% of these were accompanied by active demyelination. The duration of illness correlated with decreasing severity of active demyelination and of perivascular infiltration. Patients treated with cortico-steroids and/or immunosuppressive substances showed no or only moderate inflammatory lesions. The duration of illness in both these groups was significantly longer than the average of untreated patients. The significance of these pathological findings for the CSF cytology in multiple sclerosis is discussed.

Adrenal Cortex Hormones

Macrophage infiltration in the human retina.

The retinal tissues were examined by light microscopy and by scanning and transmission electron microscopy in a human eye in which there was extensive infiltration by macrophages. The stimulus to macrophagic infiltration was an immune response in a mixed sympathetic and lens-induced ophthalmitis which occurred after surgical treatment for glaucoma. The inflammatory infiltrate was so exuberant that the cells were considered to be predominantly exogenous and the sites of entry into the eye included the pars plana, the optic disc, and the retinal and choroidal blood vessels. Within the retina it appeared that the macrophages migrated via the nerve fibre layer and via the subretinal and subpigment epithelial spaces.

Glaucoma

Renal failure secondary to leukemic infiltration of the kidneys.

Leukemic infiltration of the kidneys is a very rare cause of renal failure. A woman with acute lymphoblastic leukemia presented with nonliguric renal failure and was found to have massively enlarged kidneys. The size of the kidneys was dramatically reduced through the combined effects of local radiation therapy and systemic chemotherapy. Because this rapid shrinkage of the kidneys was associated with improvement in renal function, the uremia was ascribed to leukemic infiltration. As a consequence of rapid tumor lysis in the presence of renal failure, marked hyperphosphatemia and hypocalcemia developed. The literature experience with renal failure secondary to leukemic infiltration of the kidneys is reviewed.

Calcium

Immunofluorescence study of lymphocytic infiltration in gliomas. Identification of T-lymphocytes.

Five human brain tumours (3 glioblastomas and 2 astrocytomas) and 5 rat brain tumours induced in Sprague--Dawley animals by systemic administration of N-methyl-N-nitrosourea (3 pleomorphic gliomas and 2 mixed gliomas) were studied. The human brain tumours were surgical specimens excised from patients with no cranial surgery prior to their disease. The experimental brain tumour had been adapted to tissue culture, propagated in vitro and then transplanted to immunocompetent and immunodeficient rats of the same stock. The above-described material was selected in consideration of the mononuclear cell infiltrates occurring in these tumours. Frozen sections of human and rat gliomas, the latter both primary and transplanted, were prepared and investigated as to the presence of T-lymphocytes within the mononuclear round cell infiltrates. This was done with the indirect immunofluorescence method using rabbit antisera against man and rat T-lymphocytes. With this technique a variable percentage of T-lymphocytes was demonstrated in the cell infiltrates of human and rat gliomas alike. The tumour transplanted in thymectomized rats showed only isolated, scattered, positive-reacting cells, i.e., cells recognizable as T-lymphocytes by the above method. The results can be interpreted as circumstantial evidence for the occurrence of tumour-specific and/or tumour-associated antigens in the parenchymal cells of spontaneous and chemically-induced gliomas.

Animals

Lichen planus: immunologic and morphologic identification of the submucosal infiltrate.

The purpose of this investigation was to specifically identify T cells, B cells, and histiocytes in the infiltrate typically seen in lichen planus. In frozen tissue sections, AET-treated sheep erythrocytes formed immunologic rosettes with the lymphocytes in the infiltrate, designating them as T cells. Rosette assays with reagent erythrocytes, IgGEA, IgMEA, IgMEAC, and E resulted in nonadherence, indicating a lack of B cells and macrophages, and indirectly implicating them as T cells. Scanning electron microscopy of the cellular infiltrate, in situ, showed that the cells had smooth, nonvillous surfaces. These observations were consistent with a T cell origin and were considered supportive of the immunologic data. The results of this investigation support the hypothesis that lichen planus is a disease mediated by thymus-dependent lymphocytes.

Connective Tissue