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Background Recent humanitarian crises have led to a call for professionalization of the humanitarian field, but core competencies for the delivery of surgical care have yet to be established. The objective of this study was to survey surgeons with experience in disaster response to identify surgical competencies required to be effective in these settings. Methods An online survey elucidating demographic information, scope of practice, and previous experience in global health and disaster response was transmitted to surgeons from a variety of surgical societies and nongovernmental organizations. Participants were provided with a list of 111 operative procedures and were asked to identify those deemed essential to the toolset of a frontline surgeon in disaster response via a Likert scale. Responses from personnel with experience in disaster response were contrasted with those from nonexperienced participants. Results A total of 147 surgeons completed the survey. Participants held citizenship in 22 countries, were licensed in 30 countries, and practiced in >20 countries. Most respondents (56%) had previous experience in humanitarian response. The majority agreed or strongly agreed that formal training (54%), past humanitarian response (94%), and past global health experiences (80%) provided adequate preparation. The most commonly deemed important procedures included control of intraabdominal hemorrhage (99%), abdominal packing for trauma (99%), and wound debridement (99%). Procedures deemed important by experienced personnel spanned multiple specialties. Conclusion This study addressed specifically surgical competencies in disaster response. We provide a list of operative procedures that should set the stage for further structured education programs. [ABSTRACT FROM AUTHOR]

Unregulated activity of interleukin (IL) 22 promotes intestinal tumorigenesis in mice. IL22 binds the antagonist IL22 subunit alpha 2 (IL22RA2, also called IL22BP). We studied whether alterations in IL22BP contribute to colorectal carcinogenesis in humans and mice. We obtained tumor and nontumor tissues from patients with colorectal cancer (CRC) and measured levels of cytokines by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. We measured levels of Il22bp messenger RNA in colon tissues from wild-type, Tnf –/–, Lta –/–, and Ltb –/– mice. Mice were given azoxymethane and dextran sodium sulfate to induce colitis and associated cancer or intracecal injections of MC38 tumor cells. Some mice were given inhibitors of lymphotoxin beta receptor (LTBR). Intestine tissues were analyzed by single-cell sequencing to identify cell sources of lymphotoxin. We performed immunohistochemistry analysis of colon tissue microarrays from patients with CRC (1475 tissue cores, contained tumor and nontumor tissues) and correlated levels of IL22BP with patient survival times. Levels of IL22BP were decreased in human colorectal tumors, compared with nontumor tissues, and correlated with levels of lymphotoxin. LTBR signaling was required for expression of IL22BP in colon tissues of mice. Wild-type mice given LTBR inhibitors had an increased tumor burden in both models, but LTBR inhibitors did not increase tumor growth in Il22bp –/– mice. Lymphotoxin directly induced expression of IL22BP in cultured human monocyte–derived dendritic cells via activation of nuclear factor κB. Reduced levels of IL22BP in colorectal tumor tissues were associated with shorter survival times of patients with CRC. Lymphotoxin signaling regulates expression of IL22BP in colon; levels of IL22BP are reduced in human colorectal tumors, associated with shorter survival times. LTBR signaling regulates expression of IL22BP in colon tumors in mice and cultured human dendritic cells. Patients with colorectal tumors that express low levels of IL22BP might benefit from treatment with an IL22 antagonist. [ABSTRACT FROM AUTHOR]

Effector functions of IgG Abs are regulated by their Fc N -glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects. We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction following immunization of mice with a foreign protein antigen and different adjuvants. Mice were analyzed for GC T-cell, B-cell, and plasma cell responses, as well as for antigen-specific serum IgG subclass titers and Fc glycosylation patterns. Different adjuvants induce distinct IgG+ GC B-cell responses with specific transcriptomes and expression levels of the α2,6-sialyltransferase responsible for IgG sialylation that correspond to distinct serum IgG Fc glycosylation patterns. Low IgG Fc sialylation programming in GC B cells was overall highly dependent on the Foxp3– follicular helper T (T FH) cell–inducing cytokine IL-6, here in particular induced by water-in-oil adjuvants and Mycobacterium tuberculosis. Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27 receptor–dependent IFN-γ+ T FH1 cells, IL-6/IL-23–dependent IL-17A+ T FH17 cells, and high ratios of T FH cells to Foxp3+ follicular regulatory T cells. Here, the 2 latter were dependent on M tuberculosis and its cord factor. This study's findings regarding adjuvant-dependent GC responses and IgG glycosylation programming may aid in the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns in the GC. [ABSTRACT FROM AUTHOR]

Objective Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income. Methods The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health as well as with experience in LMIC health care. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources. Results The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs, comprising primary health centers and first-level, referral, and tertiary hospitals. The recommendations include essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications. Conclusions The resources recommended have the potential to improve the ability of LMIC health care systems to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization, without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning prehospital and interhospital transport system, and vascular training for existing and future health care providers. [ABSTRACT FROM AUTHOR]

Summary: We present a case of pulmonary nocardiosis in a patient suffering from idiopathic thrombocytopenic purpura (ITP), an autoimmune disorder in which platelets are immunologically destroyed. ITP corticosteroid therapy, as well as the patient''s diabetes mellitus history caused immunosuppression, leading to an incidental lung infection by nocardia asteroides. The combination of pulmonary nocardiosis and ITP is, as far as we know, very rare. [Copyright &y& Elsevier]

Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels ( p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation ( p = 0.018/ p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis ( p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes ( p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.

Anti-GBM disease is a rare, life-threatening small vessel vasculitis caused by circulating anti-GBM antibodies resulting to rapidly progressive glomerulonephritis and/or pulmonary haemorrhage. The gold standard for the diagnosis is the renal biopsy with the pathognomonic finding of linear deposition of IgG along the glomerular capillaries. Early diagnosis and intervention are key determinants of the response to therapy and long-term prognosis of these patients. However, during COVID-19 pandemic recognizing a pulmonary-renal syndrome caused by autoimmune diseases has become challenging. Herein, we aimed to describe a rare case of anti-GBM disease with pulmonary haemorrhage and rapidly progressive glomerulonephritis in a young man in a tertiary referral hospital in Greece, while COVID-19 pandemic was at its peak. Although the patient presented high level of creatinine and crescents, the early diagnosis and start of treatment resulted to favourable renal prognosis., Competing Interests: The authors declare no competing interests., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

Patients with altered kidney function are at increased risk of hypocalcemia after denosumab administration. There is however a small number of studies and case reports describing hypocalcemia refractory to treatment. We describe a case of severe hypocalcemia, after the administration of three doses of denosumab, in a young patient with lupus nephritis under corticosteroid coverage and osteopenia. However, more studies are needed in order to extract a safe conclusion about the factors that contribute to the development of severe hypocalcemia in this group of patients., Competing Interests: The authors have no conflict of interest.

Background: The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV., Methods: This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared., Results: In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p  = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p  = 0.006), were more often hemodialysis dependent (64% vs. 19%, p  = 0.009) and progressed more often to ESRD (55% vs. 11%, p  = 0.01) compared to normo-complementemic patients ( n  = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62, p  = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567; p  = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p  = 0.033), low serum C3 levels (42% vs. 18%, p  < 0.001) and serious infections during follow-up (57% vs. 18%, p  = 0.047) compared to those with negative ( n  = 11) IF staining., Conclusion: Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

Touch preparations from surgically removed pituitary adenomas were studied by both routine staining and immunocytochemistry for all anterior pituitary hormones. The results were correlated with the histologic, histochemical, immunohistochemical and ultrastructural findings. Several features were recognized, some of them applicable in diagnosing various adenoma types: high cellularity, cell monomorphism, nuclear irregularities and heterogeneity of immunoreactivity, all major diagnostic criteria of pituitary adenoma. The presence of numerous fibrous bodies associated with nuclear pleomorphism, multinucleation and peripheral displacement of nuclei, in association with growth hormone (GH) immunopositivity, represent diagnostic criteria for sparsely granulated GH cell adenoma. The "Golgi" pattern of prolactin (PRL) immunopositivity in conjunction with the small size of cell and nucleus and the presence of microcalcifications represents diagnostic features of PRL-secreting adenoma. Cytoplasmic accumulation of hyaline material in association with peripheral distribution of periodic acid-Schiff stain and adrenocorticotropic hormone immunoreactivity is characteristic of sparsely granulated corticotroph cell adenoma. Knowledge and application of the described features may contribute significantly to the diagnostic approach to pituitary adenomas.

Objective: The aim of this study was to investigate the presence of interleukin-6 (IL-6) in human pituitary adenomas., Design: Immunocytochemistry was performed in 15 cases of pituitary adenomas obtained at transsphenoidal surgery., Patients: Fifteen cases of pituitary adenomas were examined; these included five GH-secreting adenomas, four prolactinomas, four ACTH-secreting adenomas and two null-cell ('functionless') adenomas., Measurements: Each tumour was stained for the presence of IL-6 by means of the avidin-biotin-peroxidase complex (ABC) technique, and was also stained for GH, prolactin, ACTH and alpha-subunit by conventional immunocytochemistry., Results: Fourteen of the 15 tumours examined, excepting one GH-secreting tumour, demonstrated clusters of IL-6 positively stained cells; the specificity of the staining was established by a significant decrease in staining in parallel sections of all tumours studied when the anti IL-6 antibody was preabsorbed with recombinant human IL-6., Conclusions: It is concluded that IL-6 immunoreactivity is present in human pituitary tumours, and is independent of the specific secretory cell product. The role of this cytokine in the pathogenesis of such tumours requires further investigation.