Cytogenetic, Clinical, Hematologic, Demographic, Immunohistochemical, and Flow Cytometry Characteristics of Patients with Plasma Cell Neoplasm in Five Years: A First Report from Iran.

Background: The aggregation of clonal plasma cells causes plasma cell neoplasms, which vary in severity and clinical outcomes. The present research focused on the epidemiological, clinical, immunologic, and cytogenetic characteristics of plasma cell neoplasms. Methods: In this five-year retrospective cross-sectional study, demographic information such as age and sex, calcium elevation, renal insufficiency, anemia, and bone lesion (CRAB) characteristics, as well as laboratory data including bone marrow and peripheral blood film results, immunohistochemistry, flow cytometry, and cytogenetic study outcomes were collected at Shiraz University of Medical Sciences, Shiraz, Iran. The collected data were analyzed using SPSS Statistics software (version 20.0). Descriptive statistics were reported as numbers, percentages, and mean±SD. Results: 417 newly diagnosed plasma cell neoplasm patients were confirmed by bone marrow or other tissue biopsy tests. 279 patients were men (66.9%). The most prevalent age group was 60-64 years old (18.46%). Plasma cell myeloma (PCM) affected 355 (85.13%) patients, while monoclonal gammopathy of undetermined significance (MGUS) affected 6 (1.43%) patients. Solitary plasmacytoma was seen in 56 (13.42%) patients. At the time of diagnosis, 119 (33.52%) of 355 PCM patients were asymptomatic, whereas 236 (66.47%) patients had at least one CRAB symptom, 55 (15.49%) had two or more, and 14 (3.94%) had three or more. There were 7 (1.97%) cases of amyloidosis. Cytogenetic abnormalities were found in 51.28% (40/78) of the patients. Twenty-one individuals (52.5%) were hyperdiploid with multiple trisomy, while 19 (47.50%) were not. Conclusion: When diagnosed, Iranian PCM patients might have more advanced disease. PCM was more prevalent in young adults, and hyperdiploid was the most common cytogenetic finding in this investigation.

Myeloid Sarcoma: Case Series with Unusual Locations.

Myeloid sarcoma (MS) or chloroma is a localized mass composed of blastic cells of granulocytic lineage. It is a subtype of acute myeloid leukemia and usually presents as a complication of acute myeloid leukemia, myeloid dysplastic syndrome, or myeloproliferative disorder. MS occurs in 2.5-9.1% of patients with AML, precedes the clinical disease, coincidence with the onset or at relapse and in rare conditions, it can occur with no evidence of hematologic disorders. Here, we presented seven cases of MS in unusual locations or with rare presentations at presentation or relapse. We concluded that MS should be considered in the differential diagnosis of any high-grade tumor, especially in a patient with previous history of any myeloid neoplasm.

Evaluation of INI1 Protein Expression Through IHC Study in Pediatric High-Grade Brain Tumors in South of Iran in 2008-2021.

Background & Objective: Brain tumors are the most frequent solid tumors in children. High-grade tumors are more challenging in diagnosis. Atypical teratoid rhabdoid tumor (ATRT) may be mistaken for other high-grade brain tumors. Molecular genetic analysis of ATRT has shown deletion and mutation in the hSNF5/INI1 gene in most of the cases. The INI1 protein expression can be helpful for the accurate diagnosis. Methods: In this study, immunohistochemical staining (IHC) using INI1 antibody was performed to determine the possibility of ATRT misdiagnosis. Totally, 147 tumors including 6 ATRTs, 81 medulloblastomas, and 60 other CNS tumors were examined in children between 0 and 17 years old. Results: No nuclear staining was found in the six ATRT cases, while most of other CNS tumors demonstrated nuclear staining. Five cases were previously diagnosed with medulloblastoma, primitive neuroectodermal tumor (PNET), and anaplastic oligodendroglioma, while the diagnoses were changed to ATRT based on the re-evaluation of the H&E slides and INI1 study. Additionally, two cases were recurrent tumors whose features were consistent with those of ATRT. The INI1 immunostaining was negative in these cases. Conclusion: INI1 was very helpful in distinguishing ATRT from its mimickers in challenging cases. All known ATRT cases in this study were immunonegative for INI1. Thus, INI1 is recommended to be used in the initial IHC panel for the high-grade brain tumors, especially in children under the age of three years, so that they can benefit from intensified therapeutic regimens.

Sporadic Lymphangioleiomyomatosis Disease: A Case Report.

Pulmonary Lymphangioleiomyomatosis (LAM) is a rare disease of the lung and lymphatic system that primarily affects women of childbearing age. LAM is a progressive disease with a terrible prognosis, which worsens over time and is extremely difficult to treat. In this study, we discuss the case of a 31-year-old woman with LAM who was initially misdiagnosed with leiomyoma and the way that led to a true diagnosis and effective treatment. Following a precise diagnosis based on comprehensive clinical data and particular immunohistochemical tests, sirolimus treatment was initiated, and the patient entirely responded to the treatment. This case report demonstrated that LAM is an uncommon condition that is challenging to diagnose, which causes its treatment to be delayed.

Philadelphia Chromosome Positive Chronic Myelogenous Leukemia Blastic Crisis in A Patient with Unusual Primary Myelofibrosis Characteristics; A Case Report.

INTRODUCTION: Myeloproliferative neoplasms (MPNs) are divided into BCR-ABL positive Chronic myeloid leukemia (CML) and BCR-ABL negative MPNs including Polycythemia vera (PV), Essential Thrombocythemia (ET) and Primary myelofibrosis (PMF). Evaluation of the Philadelphia chromosome in MPNs is a diagnostic requirement for classic CML. CASE REPORT: In 2020, a 37-year-old woman with negative cytogenetic testing for Janus kinase2 (JAK2), Calreticulin (CALR), myeloproliferative leukemia virus oncogene (MPL), and positive for BCR-ABL1 mutation with reticular fibrosis in bone marrow was diagnosed as CML. Some years ago, the patient had been diagnosed with PMF with evidence of histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD). The BCR-ABL fusion gene was initially evaluated which was negative. Then, Cutaneous squamous cell carcinoma (cSCC) was confirmed by Dermatopathologist with palpable splenomegaly and high white blood cell (WBC) count with basophilia. Finally, BCR-ABL was detected positive by the fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). In fact, the co-occurrence of PMF with CML was identified. CONCLUSION: This case study highlighted the importance of some cytogenetic methods in the detection and classification of MPNs. It is recommended that physicians pay more attention to it and be aware of the planning treatment.

Critical value in surgical pathology: evaluating the current status in a multicenter study.

BACKGROUND: The concept of critical value is not evident in surgical pathology, and there is no established protocol for determining, reporting, and documenting these results. MATERIALS AND METHODS: A questionnaire was designed regarding critical value in surgical pathology, and all pathologists and some clinicians from five laboratories were asked to participate through an invitation link. The most important items were selected, and all pathologists were instructed to follow a standard operating procedure to deal with critical results for a year. RESULTS: A total of 43 pathologists and 44 non-pathologists participated in the study. Some critical or unexpected items were selected. Most participants agreed that the optimal time to announce critical reports is within 24 h of establishing the final diagnosis, and a phone call was the most dependable communication option. In addition, the most qualified recipients were the attending physicians. Therefore, a written policy was implemented for a year. One hundred seventy-seven critical or unexpected cases (0.5%) were detected. Mucormycosis and cytomegalovirus (CMV) were the most frequent critical cases. CONCLUSION: There are no set criteria for critical items or the reporting process in surgical pathology. It is possible to establish more uniform norms for reporting these cases by boosting pertinent research efforts and recruiting more pathologists and physicians. Additionally, it is advised that each medical facility compile its own unique critical or unexpected diagnosis list.

Diagnostic Value of Epithelial Cell Adhesion Molecule Flow Cytometry for Diagnosis of Metastatic Carcinoma in Serous Effusions.

INTRODUCTION: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids. METHODS: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(-) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity. RESULTS: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively. CONCLUSION: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity.

Association of Demographic, Clinical, and Vaccination Characteristics with COVID-19 Viral Load Assessed by qRT-PCR.

BACKGROUND: The effect of vaccination on the SARS-CoV-2 baseline viral load and clearance during COVID-19 infection is debatable. This study aimed to assess the effects of demographic and vaccination characteristics on the viral load of SARS-CoV-2. METHODS: We included the patients referred for outpatient SARS-CoV-2 qRT-PCR (reverse transcriptase quantitative polymerase chain reaction) test between July and September 2022. Cycle threshold (Ct) data were compared based on the demographic and vaccination characteristics. A generalized linear model was used to determine the factors associated with the SARS-CoV-2 PCR Ct value. RESULTS: Of 657 participants, 390 (59.4%) were symptomatic and 308 (47.1%) were COVID-19 positive. Among 590 individuals with known vaccination status, 358 (60.6%) were booster vaccinated, 193 (32.6%) were fully vaccinated, 13 (2.2%) were partially vaccinated, and 26 (4.4%) were unvaccinated. Most vaccinated patients received inactivated vaccines (70.5%). The median Ct value was 20 [IQR: 18-23.75] with no significant difference between individuals with different vaccination statuses (P value = 0.182). There were significant differences in Ct value in terms of both symptom presence and onset (both P values < 0.001). Our regression model showed that inactivated vaccines (P value = 0.027), mRNA vaccines (P value = 0.037), and the presence and onset of symptoms (both P values < 0.001) were independent factors significantly associated with the viral load. CONCLUSION: The SARS-CoV-2 baseline viral load is unaffected by vaccination status, yet vaccination might accelerate viral clearance. Furthermore, we demonstrated that the presence and onset of symptoms are independent variables substantially associated with the patient's viral load.

The utility of IMP3 immunohistochemical staining in differentiating nodular lymphocyte predominant Hodgkin Lymphoma from T-Cell/Histiocyte-Rich large B-Cell lymphoma.

INTRODUCTION: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and T cell/histiocyte-rich large B-cell lymphoma (THRLBCL) have overlapping histological features that make their diagnosis challenging. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a recently proposed diagnostic marker for Hodgkin's lymphoma. The aim of this study was to determine the ability of IMP3 in differentiating NLPHL from THRLBCL. METHODS: In this retrospective study, the formalin-fixed paraffin-embedded blocks from 56 patients (28 NLPHL and 28 large B cell lymphoma (LBCL, including 16 THRLBCL and 12 DLBCL, NOS) cases based on immunohistochemistry (IHC) were included. Sample sections were stained for IMP3 using IHC method. Moderate to strong staining in at least 10% of tumor cells was considered positive IMP3 expression. RESULTS: The mean age of the patients was 41.25 ± 16.08 years old. The majority of the patients were male. There was a significant age difference between NLPHL (34.61 ± 16.44 years old) and LBCL (47.89 ± 12.85 years) groups (p = 0.001). No significant difference was seen in gender and site between NLPHL and LBCL groups. The expression of IMP3 was mainly strong in LBCL group, while it was heterogeneously distributed among NLPHL samples ranging from weak to strong (p < 0.001). It was determined that strong IMP3 expression at 55.00% can differentiate LBCL from NLPHL with 71.4% sensitivity and 71.4% specificity. CONCLUSION: Our findings showed that IMP3 may be a good complement in differentiating NLPHL cases from THRLBCL.

Concordance between TIRADS and Cytology in Thyroid Nodule.

Introduction: Palpable thyroid nodules are stated in 4 to 7% of individuals. This study was designed to evaluate the relation of Thyroid Imaging Reporting and Data System (TIRADS) and fine-needle aspiration (FNA) based cytology reports in patients with thyroid nodules. Materials and Methods: In this retrospective cross-sectional study, individuals with thyroid nodules who were selected for ultrasonographic-guided FNA enrolled in this study. Demographic data, radiologic assessment, and cytology report were gathered based on hospital medical records. TIRADS grading of the nodules was assessed for each nodule. Cytology was performed on all samples. Sensitivity and specificity were calculated by comparing cytology with ACR-TIRADS and also cytology with TIRADS 4-5 cut-off point as a radiologic malignant lesion. Results: 172 patients were studied, 151 of whom were female and 21 were male. The mean age of the patients was 49.46 years. Most of the patients had TIRADS 4 (53.5%) followed by 3 (31.4%), and 5 (11.6%). 151 patients (87.8%) had a benign lesion in cytology. Of them, 118 had colloid nodules. There was a statistically significant relation between TIRADS and cytology (p-value<0.001). Sensitivity, specificity, AUC, and positive and negative predictive value for ACR-TIRADS classification were 76.19%, 47.54%, 0.619, 20.00%, and 92.06%, respectively. These values for cut-off "4-5" classification was 86.36%, 38.00%, 0.622, 16.96%, and 95.00%. Conclusions: According to the significant concordance between TIRADS and cytology, as shown in the results of our study, it seems that TIRADS could be used to decrease the amount of unnecessary FNA in individuals with thyroid nodules.

Immunoexpression of p53 mutant-type in Iranian patients with primary and recurrence oral squamous cell carcinoma.

Mutations in tumor suppressor p53 protein can occur at different phases of malignant transformation and affect the patient's prognosis. This study aimed to evaluate the expression of mutant p53 protein in Iranian patients with the primary and recurrence oral squamous cell carcinoma (OSCC). This retrospective cross-sectional study conducted on a group of patients with the primary OSCC (n=122) and the control subjects with oral noncancerous reactive lesions (n=80). Immunohistochemistry was performed with the DO-7 monoclonal antibody against p53 protein, and samples with ≥10% immunostaining were considered positive. Statistical analyses were carried out using SPSS. Positive staining for p53 was observed in none of the control subjects and 57.4% (70 of 122) of the primary OSCC patients (p<0.0001, OR=107.69, 95%CI=6.49-179.0). The p53 immunopositivity had no significant differences between males and females (54.2% vs. 62%, p=0.390), but significantly different between those aged below and over 50 years (p<0.0001, OR=4.52, 95%CI=1.07-12.05). During follow-up, OSCC recurrence occurred in 104 patients, but the phenotype of the mutant p53 protein in patients who relapsed was the same as in matched primary tumors (p=0.763). Risk of recurrence had no significant differences between p53-positive and p53-negative cases (p=0.953), males and females (p=0.263), and age below and over 50 years (p=0.223). Despite its confirmed diagnostic value, the immunoexpression of the p53 mutant protein in OSCC in cancer recurrence was the same as in the primary tumor. However, further studies with a larger sample size and longer follow-up are needed to confirm or change our conclusions.

Expression of PD1 and PDL1 as immune-checkpoint inhibitors in mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) has remained incurable in most patients. The expression of PD-L1 as a prognostic and predictive marker has not been fully evaluated in MCL. The current study aimed to determine PD-1/PD-L1 expression in MCL specimens and its significance as an immune check point inhibitor. METHODS: This retrospective study was conducted on the formalin-fixed paraffin-embedded blocks of 79 confirmed MCL patients based on immunohistochemistry (IHC). The IHC method was used to stain patient samples for PD1 and PDL1. Positive PD-1/PD-L1 expression was defined as moderate to strong or memberanous or memberanous/cytoplasmic staining in at least 5% of tumor and/or 20% of associated immune cells. Tumor aggressiveness was determined based on Ki67 and variant. RESULTS: The mean age of the patients was 60.08 ± 10.78 years old. Majority of the patients were male. The prevalence of aggressive tumor was 25%. Positive PD1 and PDL1 expression were identified in 12 (15.0%) and 3 (3.8%) of tumor cells, respectively. PD1 and PDL1 were positive in zero (0%) and 7 (8.9%) of background cells, respectively. There was no significant difference in terms of study parameters between positive and negative groups for both PD1 and PDL1 proteins. PD1 tumor cell percentage was negatively correlated with age (r = -0.254, p = 0.046). CONCLUSION: Our results suggest that neither PD-1 nor its ligands represent relevant targets for MCL treatment. Age may impact the efficiency of immune checkpoint inhibitors and could be related to the increased incidence of MCL with age.

Carcinoma of Unknown Primary Origin: Application of Immunohistochemistry With Emphasis to Different Cytokeratin 7 and 20 Staining Patterns.

BACKGROUND: Although the primary origin of some carcinomas may be obscure to clinicians, its identification is crucial as it affects prognosis and treatment (especially novel targeted therapies). Immunohistochemistry (IHC) may be helpful in identifying the primary origin of carcinomas. This retrospective survey aimed to evaluate the frequency and accuracy of each IHC marker used to determine the origin of carcinomas. METHODS: The review of pathology department archives revealed 307 cases of cancer of unknown primary origin (CUP) between 2015 and 2020, which were accessible in the department archives. Demographic information, site of biopsy, clinical and pathologic diagnoses, and IHC results of the patients were collected. RESULTS: The patients included 157 (51.15%) men and 150 (48.85%) women. The age of the patients ranged from 14 to 92 years, including 106 (34.5%) expired cases. In 27% of cases, the primary origin of carcinoma remained unknown. The agreement between pathologic and clinical diagnoses was 59%. The most common pattern of cytokeratin (CK) expression in CUP was CK7+/CK20- (55.3%), followed by CK7-/CK20- (19%), CK7+/CK20+ (15%), and CK7-/CK20+ (10.7%), respectively. CONCLUSION: The IHC analysis may improve the diagnosis of CUPs. However, the origin of some cases remains unknown despite an IHC analysis, thereby necessitating the use of more diagnostic procedures or gene expression studies for reaching a definitive diagnosis.

Evaluation of genetic diversity of colistin-resistant Acinetobacter baumannii by BOX-PCR and ERIC-PCR: the first report.

Aim: To control the spread of Acinetobacter baumannii in hospitals, it is necessary to identify the reservoir of organisms and the way they are transmitted. This study analyzed samples by BOX-PCR and enterobacterial repetitive intergenic consensus PCR techniques. Methods: Isolated strains were identified using the Microgen kit and blaOXA-51 gene. The genetic diversity of strains that were sensitive or resistant to colistin was evaluated by BOX-PCR and enterobacterial repetitive intergenic consensus PCR methods. Results: A total of 13% of the isolates were resistant to colistin, whereas 87% of the strains were sensitive to this medication. A. baumannii strains that were resistant or sensitive to colistin were divided into five groups using the BOX-PCR method and six groups using the enterobacterial repetitive intergenic consensus PCR method. Conclusion: Rapid identification and the use of appropriate tools to control colistin-resistant clones are essential to prevent the further spread of A. baumannii.

Cytomegalovirus gastritis in a patient with severe acute respiratory syndrome coronavirus 2 infection: A case report and literature review.

In this study, we reported a previously immunocompetent patient who developed cytomegalovirus-induced gastric ulcers after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 33-year-old man was referred to our center with complaints of persistent dysphagia and odynophagia, and epigastric pain and discomfort after ingesting solids or liquids, a few days after his hospital discharge following admission to treat coronavirus disease 2019 (Covid-19). Endoscopy revealed inflammation and a whitish exudate in the esophagus, and multiple large active ulcers in the stomach. Histopathological and immunohistochemical findings were strongly suggestive of cytomegalovirus infection.

Schwannoma of the Rectosigmoid Colon.

Schwannoma is a rare tumor in the colon which originates from the peripheral nerve plexus. Most of the cases have been asymptomatic but occasionally present as an obstructive mass. Abdominal investigations are effective in some cases, but usually, they are not informative. A significant number of cases have been detected after their operation by histopathology examination. Immune and histochemical staining shows the spindle cells that have been positive for S-100 and vimentin, but negative for CD34 and smooth muscle actin. If the diagnosis of Schowannoma is confirmed preoperatively, segmental resection is recommended. In this case report, we presented a 58-year-old woman with pelvic mass and normal colonoscopy that mimic extramural large uterine myoma with extraluminal pressure effect on the rectosigmoid.

The effect of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices in rats with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, irregular menstruation, ovulatory dysfunction, and insulin resistance. Recent studies have reported the possible role of phytoestrogens in PCOS. This animal study aimed to evaluate the effects of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices on PCOS. METHODS: PCOS was induced by 1 mg/kg of letrozole in adult Sprague-Dawley rats. The rats then received normal saline (PCOS group), 150 mg/kg of metformin, or 20 mg/kg of genistein dissolved in 1% methylcellulose solution for 42 days. Body weight, the glycemic and lipid profile, and inflammatory, antioxidative, and histopathological parameters were assessed at the end of the intervention. RESULTS: Treatment with genistein significantly alleviated the increased level of fasting blood insulin (p=0.16) and the homeostatic model assessment of insulin resistance (p=0.012). In addition, the genistein group had significantly lower levels of serum malondialdehyde (p=0.039) and tumor necrosis factor-alpha (p=0.003), and higher superoxide dismutase enzyme activity (p<0.001). Furthermore, the histopathological analysis indicated that genistein administration led to an increase in luteinization and the development of fewer cysts (p<0.05). CONCLUSION: Biochemical and histopathological analyses indicated that genistein administration to rats with PCOS induced significant remission in oxidative, inflammatory, and glycemic and histopathologic parameters.

Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: A case report and a review of literature.

INTRODUCTION AND IMPORTANCE: Leiomyosarcoma (LMS) of the colon is an extremely rare and highly invasive tumor arising from the muscularis propria of the gastrointestinal tract. After the introduction of oncogenic role of KIT by immunohistochemistry (IHC), the reported cases of gastrointestinal leiomyosarcoma were highly limited. True LMS of the colon is such a rare disorder that there isn't much description of its nature. CASE PRESENTATION: We reported two very rare cases of primary leiomyosarcoma of sigmoid colon, which referred to our institution with symptoms of abdominal pain, lower GI bleeding and fatigue. After the initial investigations, both patients were diagnosed with primary LMS of sigmoid colon that underwent laparoscopic tumor resection. CLINICAL DISCUSSION: The classical colonic LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, and weight loss. The most common location for colonic LMS is the sigmoid colon, and ascending colon. The prognostic factors for the disease outcome have not been established properly; however, patient age, tumor size/grade, and local/distant dissemination are of great importance. CONCLUSION: Herein, we reported two rare cases of primary leiomyosarcoma of sigmoid colon that was treated with laparoscopic surgery.

Curcumin-incorporated crosslinked sodium alginate-g-poly (N-isopropyl acrylamide) thermo-responsive hydrogel as an in-situ forming injectable dressing for wound healing: In vitro characterization and in vivo evaluation.

Sodium alginate products have been extensively used for wound-dressing. In present study, a series of thermo-sensitive cross-linked poly(N-isopropylacrylamide) grafted sodium alginate (Alg-g-pNIPAM) copolymers were synthesized for delivery of curcumin to wound. FTIR, 1H NMR, elemental analysis and DSC showed successful polymerization and precise structure of copolymers. Thermogelation at 27-42 °C depending on the copolymer concentration, chain-length of pNIPAM and pH was observed. The optimum copolymer with proper rheological and syringeability properties showed excellent thermogelling at a wide range of pH and concentration, and could prolong the release of curcumin up to 72 h. In-vivo wound contraction and histopathological evaluations revealed that in addition to the higher efficacy in wound contraction, the curcumin formulation (Cur-F) significantly reduced the inflammation, enhanced the collagenesis and resulted in increased number of fibroblasts. Well-known anti-oxidant and anti-inflammatory properties of curcumin and in situ-forming nature of Alg-g-pNIPAM can make the system an excellent candidate for further investigations.

Successful treatment of acute promyelocytic leukemia in a patient with prosthetic heart valves: a case report and review of the literature.

BACKGROUND: Although life-threatening hemorrhage is a usual manifestation of acute promyelocytic leukemia (APL), thrombotic events seem to be more common in APL compared to other subtypes of acute leukemia. The treatment and prophylaxis of thrombosis are controversial due to the high risk of bleeding caused by disseminated intravascular coagulation (DIC) and thrombocytopenia. To the best of our knowledge we report the first case of APL in a patient with prosthetic heart valves successfully treated with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). We hope this case report helps clinicians to manage different spectra of coagulopathy in APL successfully. CASE PRESENTATION: A 38-year-old Asian man presented with diagnosis of APL confirmed by bone marrow biopsy. He was on warfarin due to prosthetic mitral and aortic valves. He was at risk of both hemorrhagic events due to DIC and life-threatening valve thrombosis. Our management regimen included unfractionated heparin adjusted according to the platelet count to prevent both valve thrombosis and bleeding events. The patient tolerated treatment well without any hemorrhagic or thrombotic events, and complete molecular remission was achieved by ATRA and ATO without the need for chemotherapeutic agents. CONCLUSION: Although this case is exceptional, a precise evaluation may be needed to select the appropriate dose and type of anticoagulant to treat a patient with APL.