Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Excess of the NF-ĸB p50 subunit generated by the ubiquitin ligase KPC1 suppresses tumors via PD-L1- and chemokines-mediated mechanisms.

Nuclear factor-ĸB (NF-ĸB) transcription factor is a family of essential regulators of the immune response and cell proliferation and transformation. A typical factor is a heterodimer made of either p50 or p52, which are limited processing products of either p105 or p100, respectively, and a member of the Rel family of proteins, typically p65. The transcriptional program of NF-ĸB is tightly regulated by the composition of the dimers. In our previous work, we demonstrated that the ubiquitin ligase KPC1 is involved in ubiquitination and proteasomal processing of p105 to generate p50. Its overexpression and the resulting high level of p50 stimulates transcription of a broad array of tumor suppressors. Here we demonstrate that additional mechanisms are involved in the p50-mediated tumor-suppressive effect. p50 down-regulates expression of a major immune checkpoint inhibitor, the programmed cell death-ligand 1 (PD-L1), both in cells and in tumors. Importantly, the suppression is abrogated by overexpression of p65. This highlights the importance of the cellular quantities of the two different subunits of NF-ĸB which determine the composition of the dimer. While the putative p50 homodimer is tumor-suppressive, the "canonical" p50p65 heterodimer is oncogenic. We found that an additional mechanism is involved in the tumor-suppressive phenomenon: p50 up-regulates expression of the proinflammatory chemokines CCL3, CCL4, and CCL5, which in turn recruit into the tumors active natural killer (NK) cells and macrophages. Overall, p50 acts as a strong tumor suppressor via multiple mechanisms, including overexpression of tumor suppressors and modulation of the tumor microenvironment by recruiting active immune cells.

Early histological findings may predict the clinical phenotype in Crohn's colitis.

BACKGROUND AND AIMS: Predicting the clinical course of Crohn's disease (CD) is relevant for treatment selection. Currently, such diagnostic tools are lacking. In a previous pilot study, morphometric tissue image analysis showed promise in predicting the clinical phenotype and need for surgery. In this study, we aimed to validate our previous results on a larger cohort. METHODS: Colonic biopsies from CD patients with colonic or ileocolonic disease and at least five years of post-biopsy clinical follow-up were analyzed. The results were used to predict post-biopsy clinical phenotypes and outcomes. Data analysis was performed using multivariate regression models, discriminant score (DS) computations and Neural Network (NNET). RESULTS: Multivariate analysis of morphometric variables differentiated between B1 and B2 phenotypes (sensitivity 81%, specificity 74%, accuracy on cross-validation 75%; area under the curve (AUC) of 0.74 (CI 0.6-0.84; NNET model sensitivity 87%, specificity 67% on the testing population)). Differentiation between B1 and B3 phenotypes was also possible (sensitivity 69%, specificity 76%, accuracy 70.5% on cross-validation; AUC 0.78 (CI 0.68-0.89); NNET model sensitivity 78%, specificity 77% on the testing population)). Differentiating between B2 and B3 phenotypes was not possible using morphometric variables. Multivariate analysis predicted surgery (sensitivity 67%, specificity 72.5%, accuracy 69%; AUC 0.72 (CI 0.61-0.82); NNET model sensitivity 80%, specificity 91% on the testing population)). CONCLUSIONS: This study validates previous results and suggests that morphometric image analysis of early biopsies from Crohn's colitis patients may contribute to the prediction of future outcomes such as clinical phenotype and surgery. Prospective validation on larger cohorts is still needed.

Diffuse Large B Cell Lymphoma Mimicking Granulomatosis with Polyangiitis.

In a patient with systemic multiorgan disease with overlapping features, the differential diagnosis included infectious diseases, malignancies, and systemic autoimmune or inflammatory diseases. We present an unusual case of a young male with B cell lymphoma who presented with symptoms mimicking systemic vasculitis and review the existing literature.

Expression of heparanase in soft tissue sarcomas of adults.

BACKGROUND: Heparanase is an endo-ß-D-glucuronidase that cleaves heparan sulfate chains of proteoglycans, resulting in the disassembly of the extracellular matrix. Heparanase has a central role in the development of various tumors, and its expression has been associated with increased tumor growth, angiogenesis and metastasis, but there is insufficient information about the function of heparanase in sarcomas. STUDY AIMS: 1) To evaluate heparanase levels in adult soft tissue sarcomas (STS); 2) To examine the correlation between heparanase levels and pathological and clinical parameters and treatment outcome. METHODS: Pathological specimens of primary or metastatic STS were subjected to immunohistochemical analysis applying an anti-heparanase antibody. The clinical and the pathological data, together with the data of heparanase levels, were evaluated in a logistic regression model for tumor recurrence and survival. RESULTS: One hundred and one samples were examined, 55 from primary tumors and 46 from metastatic sites. A high expression of heparanase was observed in 29 (52.7%) and 22 specimens (47.8%), respectively. There was no statistically significant difference between heparanase expressions in the primary vs. metastatic sites of tumors. Moreover, no correlation was observed between heparanase staining and tumor aggressiveness, tumor recurrence or patient survival in various groups of patients. CONCLUSION: Expression of heparanase was observed in 50% of the STS, in various histological subtypes. A larger study with homogenous groups of specific sub-types of STS or stages of disease is required to validate over-expression of heparanase as a marker of disease aggressiveness.

Alginate-PLL cell encapsulation system Co-entrapping PLGA-microspheres for the continuous release of anti-inflammatory drugs.

In spite of advances in cell microencapsulation technology in the past three decades, this approach still suffers from obstacles associated with its biocompatibility. We hypothesized that encapsulation system, which incorporates polymeric particles releasing anti-inflammatory drug in addition to the encapsulated cells, will result in improved biocompatibility, thus improving therapeutic efficacy. We have developed, optimized and studied a combined microencapsulation system in which Ibuprofen loaded PLGA microspheres (MS) are co-entrapped with cells. The combined system was developed and optimized in terms of Ibuprofen release profile, and the survival and proliferation of the co-encapsulated cells. The biocompatibility of the system was evaluated in vitro and in vivo. The developed system was shown to release Ibuprofen within two weeks, and support long-term cell viability. The combined system had improved the biocompatibility within the release period of Ibuprofen. All together, the co-encapsulation of anti-inflammatory loaded MS along with cells offers a clear advantage in the development of effective, long lasting cell based drug delivery systems. The choice of the anti-inflammatory agent, or combination of several anti-inflammatory agents needs to be carefully optimized, as well as their release profile to achieve long- term biocompatibility.

Myofibroblasts in pulmonary and brain metastases of alveolar soft-part sarcoma: a novel target for treatment?

Alveolar soft-part sarcoma (ASPS) is a rare neoplasm with chromosomal translocation that results in ASPL-TFE3 fusion. It is a slow-growing lesion associated with a high incidence of pulmonary and brain metastases indicating poor survival. We demonstrated that the ASPS metastases include also stromal myofibroblasts. These cells proliferate, express smooth-muscle genes, and synthesize extracellular matrix proteins, all of which are characteristics of activated myofibroblasts. The tumor cells also exhibited stromal components such as transforming growth factor beta (TGFbeta)-dependent, hypoxia-regulated cytoglobin (stellate cell activation association protein, cytg/STAP) and prolyl 4-hydroxylase, a collagen cross-linking enzyme. The pulmonary ASPS myofibroblasts synthesize serum response factor (SRF), a repressor of Smad3-mediated TGFbeta signaling essential for myofibroblast differentiation and Smad3. The phosphorylated active Smad3 was found mostly in the tumor cells. The brain tumor cells express cytg/STAP, but in contrast to the lung metastases, they also express SRF, Smad3, and phospho-Smad3. Halofuginone, an inhibitor of myofibroblasts' activation and Smad3 phosphorylation, inhibited tumor development in xenografts derived from renal carcinoma cells harboring a reciprocal ASPL-TFE3 fusion transcript. This inhibition was associated with the inhibition of TGFbeta/SRF signaling, with the inhibition of myofibroblasts' activation, and with the complete loss in TFE3 synthesis by the tumor cells. These results suggest that the myofibroblasts may serve as a novel target for treatment of ASPS metastases.

Diagnosing acute appendicitis in adults: accuracy of color Doppler sonography and MDCT compared with surgery and clinical follow-up.

OBJECTIVE: The objective of our study was to evaluate the accuracy of color Doppler sonography and contrast-enhanced MDCT in the diagnosis of acute appendicitis in adults and their utility as a triage tool in lower abdominal pain. MATERIALS AND METHODS: We reviewed the medical records of 420 consecutive adult patients, 271 women and 149 men, 18 years old or older, referred from the emergency department to sonography examination for clinically suspected acute appendicitis between January 2003 and June 2006. Patients underwent sonography of the right upper abdomen and pelvis followed by graded compression and color Doppler sonography of the right lower quadrant. CT was performed in 132 patients due to inconclusive sonography findings or a discrepancy between the clinical diagnosis and the sonography diagnosis. Sonography and CT reports were compared with surgery or clinical follow-up as the reference standard. Statistical analyses were performed by Pearson's chi-square test and cross-tabulation software. RESULTS: Sonography and CT correctly diagnosed acute appendicitis in 66 of 75 patients and in 38 of 39 patients, respectively, and correctly denied acute appendicitis in 312 of 326 and in 92 of 92 patients. Sonography was inconclusive in 17 of 418 cases and CT, in one of 132 cases. Sonography and CT allowed alternative diagnoses in 82 and 42 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for sonography were 74.2%, 97%, 88%, 93%, and 92%, respectively, and for CT, 100%, 98.9%, 97.4%, 100%, and 99%. CONCLUSION: Sonography should be the first imaging technique in adult patients for the diagnosis of acute appendicitis and triage of acute abdominal pain. CT should be used as a complementary study for selected cases.

Infant anaplastic lymphoma: case report and review of the literature.

Anaplastic large cell lymphoma (ALCL) is a well-known entity, but there are no data on prognosis according to the age of the patient, especially in infants. A 2-month-old girl was admitted with a 2-week history of coughing, fever, and lymphadenopathy. Physical examination revealed mild respiratory distress, an erythematous macular rash on her trunk, massive cervical lymphadenopathy, splenomegaly, and very mild ascites. Chest radiograph showed bilateral pulmonary infiltrates, pleural effusion, and a mediastinal mass. CBC count showed WBC: 172,000/microL (PMN 40%, lymphocytes 47%, monocytes 3%); hemoglobin concentration: 8.7 g/dL; platelets: 390,000/microL. Cervical lymph node biopsy revealed anaplastic lymphoma with positive staining to ALK 1 and TIA 1. Immunophenotypic analysis of peripheral and bone marrow lymphoid cells showed an aberrant T-cell immunophenotype, including expression of CD3, CD45R0+, CD43+, and CD30+. Cytogenetic analysis performed on blood and bone marrow samples demonstrated the translocation t(2;5) (p23;q35), and trisomy 47. After leucophoresis, the child received chemotherapy according to the ALCL-99-EICNHL protocol, and was started on corticosteroids and cyclophosphamide, which resulted in marked improvement. After the second course, WBC decreased to 6000/microL without tumor lysis syndrome, but the child developed bacterial and fungal disseminated infections and died of septic shock with multiorgan failure. This report is of a rare case of infant anaplastic lymphoma and excellent response to treatment. Unfortunately, she did succumb to overwhelming infection. More reports of similar cases may determine the cause and prognosis of such children, helping to tailor therapy according to the age of the child and other prognostic factors, especially bone marrow involvement.

Expression of the pro-apoptotic protein ARTS in astrocytic tumors: correlation with malignancy grade and survival rate.

BACKGROUND: Apoptosis (i.e., programmed cell death) plays a major role in the development of astrocytic tumors, which are the most common tumors of the central nervous system. ARTS, a proapoptotic protein that is localized in the mitochondria, promotes apoptosis by functioning as an XIAP antagonist and a caspase activator. METHODS: To investigate the role of ARTS in astrocytoma, the authors examined protein expression and apoptotic activity in 72 astrocytic tumors, which included low-grade astrocytomas, anaplastic astrocytomas, and glioblastomas. RESULTS: Whereas normal astrocytes did not express the ARTS protein, astrocytoma cells strongly expressed ARTS, and the expression of this protein increased with increasing tumor grade. Furthermore, increased levels of ARTS were significantly associated with higher rates of apoptosis (as measured using the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end-labeling [TUNEL] assay as well as an immunohistochemical staining assay for active caspase-3) in these tumors. Levels of two other apoptosis-related proteins, p53 and Bcl-2, also were examined using immunohistochemical methods; ARTS expression was found to be positively correlated with expression of the former and negatively correlated with expression of the latter, which is known to possess antiapoptotic activity. CONCLUSIONS: The results of the current study suggest that ARTS levels reliably reflect the ability of cells to undergo apoptosis, which serves as a defense mechanism against the development and progression of astrocytoma. Furthermore, ARTS expression, when taken into consideration in combination with tumor grade, was the only independent predictor of survival identified in the current analysis. Thus, the authors conclude that ARTS may possess utility as a prognostic marker, as well as a therapeutic tool, for patients with astrocytoma.

Growing Teratoma syndrome treated by interferon alpha-2beta: case report and literature review.

A 14-year old girl was diagnosed as suffering from an immature teratoma. As removal of the teratoma was technically unfeasible, the patient was started on interferon alpha2beta, 3 MU/day, 5 days per week. On this therapy, the growth of the teratoma was stopped and the patient has been well for the past 50 months. She continues to be treated with interferon alpha2beta, with almost no side effects and no restrictions of her everyday activities, with a good quality of life. She is able to attend school regularly, travels abroad frequently, and participates fully in everyday activities normal for her age and social conditions. Her Karnofsky performance status is 100. This case demonstrates the efficacy of interferon alpha2beta therapy in certain instances of growing teratoma syndrome, even when the tumorous mass is initially quite large.

Prognostic role of apoptotic, Bcl-2, c-erbB-2 and p53 tumor markers in salivary gland malignancies.

OBJECTIVE: The clinical characteristics and survival probability rate of 36 patients with salivary gland malignancies and 10 patients with benign salivary tumors were summarized in relation to the immunohistological analysis of the tumor, apoptotic-related markers and apoptosis rate. The expression of the markers examined - Bcl-2, c-erbB-2, p53 - was detected in paraffin sections of the tumors by the streptavidin-biotin peroxidase method following heat-induced antigen retrieval, and the apoptosis rate was determined by the TUNEL method. RESULTS: The overall 5-year survival probability was 61% for patients with malignant tumors and 100% for those with benign tumors. The survival probability of patients over 60 at diagnosis was significantly lower than that of younger patients. Patients whose malignant tumors were larger than 2 cm at diagnosis had worse survival than those with smaller tumors. The survival probability of patients whose malignant tumors were located in the submandibular glands was significantly lower than that of patients whose malignancies were located in the parotid and minor salivary glands. The survival probability of patients who demonstrated positive staining for c-erbB- 2 or TUNEL was lower than for those with negative staining. Gender, the existence of concomitant non-salivary malignancies and ethnic origin had no significant impact on survival. CONCLUSIONS: Our results demonstrated significant positive staining in the salivary tumorigenic tissue but not in the surrounding non-tumorigenic tissue examined for TUNEL, c-erbB-2, Bcl-2 and p53, pointing to a biological role for all four markers in the tumorigenic process which is yet to be elucidated. Significant reduction in survival was related to the specific location of the tumor in the submandibular gland, its size and older age of patient. Survival was also found to be significantly reduced when positive staining was demonstrated in the tumor tissue for TUNEL or c-erbB-2, more so for concomitant positive staining of both markers. Clinically, the most important result of the current study is that the survival rate of the patients examined with salivary tumors larger than 2 cm, with positive staining for both TUNEL and c-erbB-2, was 0 (p = 0.0001)!

Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological characteristics in a retrospective study.

In the current study, we examined the clinical characteristics and survival probability rates of 116 patients treated for squamous cell carcinoma (SCC) of the tongue. In 55 randomly selected patients these data were correlated with the immunohistological analysis of the tumor and apoptosis-related markers, p53, Bcl-2, c-erbB-2 (Her-2/neu), and to the apoptosis rate assessment by the terminal dUTP nick-end-labeling (TUNEL) method. The overall 5-year survival probability was 55%, which might be the result of the low incidence of smoking and/or alcohol consumption among the patients (21%), the early diagnosis (65% at Stages I-II) and the low histological grades (91% good-moderate). Radiotherapeutic or surgical treatment of the neck did not alter the survival probability achieved by local surgery for Stage I patients, but significantly improved survival for Stage II patients. Independent tumor-related variables which significantly worsened the probability of survival were found. Concomitant non-oral cancer was found to be a poor variable for prognosis prediction. Positive staining of p53, TUNEL (apoptosis rate), c-erbB-2 and Bcl-2 was found in 60, 48, 18 and 15% of the lesions, respectively (P<0.0001). The possible biological significance of these markers in tongue SCC is discussed in relation to the current literature, and an independent role for TUNEL and p53 is suggested.