Chronic Cinacalcet improves skin flap survival in rats: the suggested role of the nitric oxide pathway.

Cinacalcet is a calcimimetic medicine that has been used to treat secondary hyperparathyroidism and parathyroid cancer. Various studies have proposed the positive role of calcium and its receptor in skin wound healing. Furthermore, Cinacalcet interacts with other skin repair-related mechanisms, including inflammation and nitric oxide pathways. The present study evaluated the effect of Cinacalcet on the random-pattern skin flap survival. Eighty-four Wistar male rats were used. Multiple doses of Cinacalcet (30, 3, 1, 0.3, and 0.05 mg/kg) were used in 3 different routes of administration before the surgery. Histopathological evaluations, quantitative assessment of IL-6, TNF-α, and nitric oxide (NO), and the expression of calcium-sensing receptor (CaSR) and E-cadherin were evaluated in the skin tissue. To assess the role of NO, a NO synthase inhibitor, N-nitro-L-arginine methyl ester hydrochloride (L-NAME), was used, and histopathological effects were investigated. Cinacalcet pretreatment at the IP chronic 1 mg/kg dose significantly increased the skin flap survival rate and enhanced the NO tissue level compared to the control. However, the administration of L-NAME abolished its protective effects. IP Chronic 1 mg/kg of Cinacalcet could also decline the levels of IL-6 and TNF-α and also increase the expression of CaSR and E-cadherin in the flap tissue compared with the control group. Chronic Cinacalcet at 1 mg/kg could improve skin flap survival, probably mediated by the CaSR, NO, and inflammation-related pathways.

A case of pituitary gland abscess associated with granulomatous hypophysitis.

BACKGROUND: Granulomatous hypophysitis is a rare disease that presents with chronic inflammation of the pituitary gland. In this study, we reported a case of granulomatous hypophysitis associated with a pituitary abscess. CASE PRESENTATION: A 39-year-old woman presented with a 2-year history of infertility. For the past six months, she has suffered from amenorrhea, decreased libido, headaches, and vertigo. She was referred to our hospital with a suspected diagnosis of nonfunctioning pituitary adenoma based on her presentation and brain MRI findings. She underwent trans-sphenoidal surgery (TSS). Direct observation during surgery revealed drainage of malodor pus and pituitary gland abscess. The histopathological evaluation also showed granulomatous hypophysitis and neutrophilic microabscess formation. The patient was initially treated with high doses of ceftriaxone (2 g twice daily) and metronidazole (500 mg (mg) four times per day). Also, the patient received cortisol replacement therapy after the operation. After obtaining the antibiogram and culture results, the treatment regimen was continued for 4 weeks postoperatively, followed by amoxicillin-clavulanate (500/125 mg three times daily) for a total duration of 12 weeks. CONCLUSION: The patient recovered uneventfully and the postoperative MRI was normal without any remnant lesions.

Contralateral tinnitus and hearing loss due to a tumor at the region of inferior colliculus: illustrative case.

BACKGROUND: Subjective hearing loss resulting from unilateral lesions of the quadrigeminal cistern region or inferior colliculus is a rare entity. OBSERVATIONS: The authors presented the case of a 32-year-old man with a history of 4 months of nonpulsatile tinnitus and 1 month of unilateral sensorineural hearing loss. He was otherwise healthy with no significant previous medical history. Intravenous gadolinium contrast magnetic resonance imaging of the head revealed a lesion at the region of the left inferior colliculus suggestive of a lipoma. The tumor was removed, and the patient had no significant hearing change afterward, with an improvement in tinnitus. The histological examination demonstrated the tumor as a fibrolipoma. LESSONS: Contralateral subjective hearing loss is an uncommon presentation for a lesion in the region of the inferior colliculus.

Hypertrophic lichen planus on lip mimicking SCC.

The lichen planus (LP) is an inflammatory and immune-mediated disorder that can affect the hair, mucous membranes, nails, and skin. Lichen planus rarely affects the lips. In cases of lip involvement, it presents as radiated streaks, lace-like papules, and erosions. There is no report of lip LP presenting as hypertrophic plaque. Here, we report interesting and rare clinical presentations of LP in a 45-year-old male patient that presented with a verrucous hyperkeratotic plaque on the lower lip mimicking squamous cell carcinoma. However, oral examination revealed, reticulated white patches on the bilateral buccal mucosa, and a biopsy of the lip lesion revealed lichenoid dermatitis which led to the diagnosis of hypertrophic lichen planus. Familiarity with the different clinical presentations of LP and its variants is essential for prompt diagnosis and effective treatment.

Intracranial Rosai Dorfman Disease Presented With Multiple Huge Intraventricular Masses: A Case Report.

Introduction: Rosai-Dorfman disease (RDD) usually presents with painless cervical lymphadenopathy during the two first decades of life, with or without extranodal involvement. Exclusive extranodal manifestation, and especially central nervous system (CNS) involvement, is uncommon. The etiology remains unknown and definitive diagnosis is based on characteristic histopathological and immunohistochemical features showing S100(+) CD1a(-) RDD type histiocytes with emperipolesis. Most CNS cases are dural-based masses. Case Presentation: Herein, we present a case of RDD in an 8-year-old boy, who presented with multiple huge intraventricular masses. Conclusion: Regarding rare CNS involvement and lack of established evidence-based therapeutic approaches, reports of any individual case can supply further beneficial data concerning treatment approaches and long-term effectiveness of therapeutic strategies.

Evaluation of the association between human herpes virus 6 (HHV-6) and Hashimoto's thyroiditis.

Background and Objectives: Hashimoto's thyroiditis is a chronic inflammation and an autoimmune disease of the thyroid gland that causes hypothyroidism. Genetic, internal, and environmental factors are the causes of this disease. Because human herpes viruses such as herpesvirus type 6 (HHV-6) are involved in some autoimmune disorders, they may also play a role in causing this disease. This study aimed to evaluate the association between human herpes virus 6 (HHV-6) with Hashimoto's thyroiditis. Materials and Methods: In the present study, 64 samples of thyroid paraffin tissue including 32 samples of thyroid paraffin tissue of healthy individuals as control, and 32 samples of thyroid paraffin tissue of Hashimoto's thyroiditis patients were taken from the pathology department of Loghman Hakim Hospital in Tehran. A questionnaire collected demographic information of patients. After DNA extraction from the samples, the nested-PCR technique was performed using specific primers for HHV-6. Results: Totally, the HHV6-DNA was found in 34.4% of thyroid tissues of healthy individuals (81.8% female and 18.2% male) and 46.9% of patients with Hashimoto's thyroiditis (73.3% female and 26.7% male). It was found that this difference in virus frequency between the two groups was not statistically significant (P value=0.309). There was also no statistically significant relationship between the prevalence of human herpesvirus type 6 and age or sex. Conclusion: Based on the present study, the number of HHV-6-infected individuals in Hashimoto's patients and controls did not differ significantly; therefore, HHV-6 appears not to be associated with Hashimoto's thyroiditis.

Unusual presentation of the germinoma: A 26-year-old female.

BACKGROUND: Germinoma is a rare lesion found commonly in the pineal and suprasellar regions of the brain. Clinical presentation mainly involves the location and size of the tumor and the patient age. Endocrine abnormalities are the most common symptom. CASE PRESENTATION: The patient was a 26-year-old Iranian female who suffered from germinoma for a long time and was referred to Loghman Hakim Hospital for amenorrhea, polyuria, and polydipsia. Despite diagnostic challenges, she was finally diagnosed with suprasellar germinoma after endoscopic transsphenoidal surgery, followed by radiotherapy and medical interventions to complement the surgery. CONCLUSION: It is important to be able to diagnose the patient's problem at an early stage based on their history, hormonal profile, laboratory results and radiological view.

Case Report: Chemotherapy Indication in a Case of Neurofibromatosis Type 1 Presenting Optic Pathway Glioma: A One-Year Clinical Case Study Using Differential Tractography Approach.

Neurofibromatosis type 1 (NF1) is associated with peripheral and central nervous system tumors. It is noteworthy that the regions in which these tumors frequently arise are the optic pathways (OPs) and the brainstem. Thus, we decided to trace the procedure of diffusion Magnetic Resonance Imaging (dMRI) alterations along with Short-Wavelength Automated Perimetry (SWAP) examinations of the OPs after surgery and chemotherapy over 1 year, which enabled us to evaluate chemotherapy's efficacy in an NF1 patient with an OP tumor. In this study, a 25-year-old woman with NF1 and left optic radiation (OR) glioma underwent surgery to remove the glioma. Immunohistochemistry (IHC) revealed a Pilocytic Astrocytoma (PA) WHO grade I. Post-operation chemotherapy done using nine treatment cycles of administering Temozolomide (TMZ) for 5 days every 4 weeks. Applying the region of interest (ROI) differential tractography method and SWAP four times every 3 months allowed us to follow the patient's visual acuity alterations longitudinally. The differential deterministic tractography method and statistical analyses enabled us to discover the white matter (WM) tracts anisotropy alterations over time. Furthermore, statistical analyses on the SWAP results along time illustrated possible alterations in visual acuity. Then, we could compare and associate the findings with the SWAP examinations and patient symptoms longitudinally. Statistical analyses of SWAP tests revealed a significant improvement in visual fields, and longitudinal differential tractography showed myelination and dense axonal packing in the left OR after 1 year of treatment. In this study, we examined an old hypothesis suggesting that chemotherapy is more effective than radiotherapy for NF1 patients with OP gliomas (OPGs) because of the radiation side effects on the visual field, cognition, and cerebrovascular complications. Our longitudinal clinical case study involving dMRI and SWAP on a single NF1-OPG patient showed that chemotherapy did not suppress the OP myelination over time. However, it should be noted that this is a clinical case study, and, therefore, the generalization of results is limited. Future investigations might focus on genetic-based imaging, particularly in more cases. Further, meta-analyses are recommended for giving a proper Field Of View (FOV) to researchers as a subtle clue regarding precision medicine.

Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19.

BACKGROUND: The scientific evidence concerning pathogenesis and immunopathology of the coronavirus disease 2019 (COVID-19) is rapidly evolving in the literature. To evaluate the different tissues obtained by biopsy and autopsy from five patients who expired from severe COVID-19 in our medical center. METHODS: This retrospective study reviewed five patients with severe COVID-19, confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and imaging, to determine the potential correlations between histologic findings with patient outcome. RESULTS: Diffuse alveolar damage (DAD) and micro-thrombosis were the most common histologic finding in the lung tissues (4 of 5 cases), and immunohistochemical (IHC) findings (3 of 4 cases) suggested perivascular aggregation and diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes. Two of five cases had mild predominantly perivascular lymphocytic infiltration, single cell myocardial necrosis and variable interstitial edema in myocardial samples. Hypertrophic cardiac myocytes, representing hypertensive cardiomyopathy was seen in one patient and CD4+ and CD8+ T lymphocytes were detected on IHC in two cases. In renal samples, acute tubular necrosis was observed in 3 of 5 cases, while chronic tubulointerstitial nephritis, crescent formation and small vessel fibrin thrombi were observed in 1 of 5 samples. Sinusoidal dilation, mild to moderate chronic portal inflammation and mild mixed macro- and micro-vesicular steatosis were detected in all liver samples. CONCLUSION: Our observations suggest that clinical pathology findings on autopsy tissue samples could shed more light on the pathogenesis, and consequently the management, of patients with severe COVID-19.

The Frequency of Human Papillomavirus Positivity in Iranian Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND & OBJECTIVE: Human papillomavirus (HPV) has been associated with prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Similar to the global studies, different prevalence rates of this viral infection have been reported in Iran. Therefore, we aimed to report the prevalence of this virus and its significance in HNSCC patients. METHODS: Patients who were referred to the five hospitals of Tehran city from May 2018 to May 2019 were enrolled in this study. All patients were diagnosed with HNSCC based on pathologic study. The pathologic disease staging was defined, and DNAs were extracted from the fresh tissue samples via kits. After polymerase chain reaction (PCR), HPV positive samples were evaluated for determining genotypes and data analysis. RESULTS: Of the 46 patients, three patients (6.5%) showed positive HPV results with the following subtypes: 18 (in two patients), 52 (in three patients), 61 (in two patients), 67, and 73.Comparison of variables between the groups with and without HPV showed a significant difference based on the tumor's lymphatic invasion (P=0.041), peripheral lymph node involvement (P=0.008), and histologic grade (P=0.011), but no statistically significant difference in terms of other variables such as age, primary tumor site, size, pathologic stage, vascular or perineural invasion, metastasis, smoking, and alcohol consumption was found.

The diagnostic value of p63, p16, and p53 immunohistochemistry in distinguishing seborrheic keratosis, actinic keratosis, and Bowen's disease.

Seborrheic keratosis (SK), actinic keratosis (AK), and Bowen's disease (BD) are squamoproliferative disorders of the skin. Histologically, they may mimic each other and therefore, they might be misinterpreted, especially in small samples. The aim of this study is to clarify the expression of p63, p16, and p53 proteins in SK, AK, and BD and evaluate the efficacy of these markers in order to distinguish between the aforementioned lesions. A total of 46 cases were collected (15 SK, 16 AK, and 15 BD) and stained for p63, p16, and p53. The stain intensity and the cell distribution labeling were scored and then analyzed by SPSS software. All cases of BD which became positive for p53 revealed basal keratinocytes sparing. Instead, all or nearly all basal keratinocytes in AK cases were positive for this marker. These were also seen in p16 staining results and they were between AK and BD (P = .024). Our study demonstrates p16 and p53 are useful markers in separating AK and BD according to basal keratinocytes involvement and sparing, respectively.

Cytomegalovirus-induced cutaneous ulcer mimicking vasculitis in a patient with systemic lupus erythematous: A case report and review of the literature.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which can be complicated with cytomegalovirus (CMV) infection during its course. CMV reactivation can mimic an SLE flare and lead to delay in diagnosis. Here, we reported a previously diagnosed SLE patient who presented with fever, leukopenia, and cutaneous ulcers. Initially, this was diagnosed as an SLE flare and the patient was treated with higher doses of corticosteroids but no improvement was observed. Both nuclear and cytoplasmic inclusions inside the endothelial cells in the skin biopsy as well as positive immunohistochemistry (IHC) staining for CMV antigen were clues to the correct diagnosis of CMV reactivation. Treatment with ganciclovir resulted in clinical resolution. In this report, a very rare clinical form of CMV infection manifesting as cutaneous necrotizing vasculitis on the lower extremity is described and the literature regarding this case is reviewed.

Lepromatous leprosy presenting with type II reaction before and type I reaction after treatment.

Lepromatous leprosy is associated with a high bacillary load and poor cellular immune response. Early dermatologic manifestations include erythematous macules, papules, nodules, and plaques with a symmetrical distribution. Leprosy also shows two major reaction states including type I (reversal reaction) and type II (vasculitis). These reactions are usually seen in some patients who are undergoing treatment. Herein, we report an interesting patient with lepromatous leprosy who presented with skin lesions of type II reaction without receiving any anti-leprosy treatment and surprisingly showed a type I reaction eight months after the beginning of the treatment.

Primary Kaposi sarcoma of the glans: A rare case in an HIV-negative patient.

First presentation of the Kaposi sarcoma (KS) on the penis is not prevalent, and it was reported in 2%-3% of the cases that mostly occurred in the HIV-positive patients. Here, we report a case of primary KS on the glans penis in an HIV-negative patient.

No evidence of occult HBV infection in population born after mass vaccination.

Despite access to efficient hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV infection remains a global health concern. HBV infection has decreased by this program. Nevertheless, breakthrough infections occur due to generation of occult HBV infection (OBI) and surface gene mutants in the immunized population. We aimed to determine the presence of OBI in a population born after initiation of nationwide HBV vaccination in Tehran, Iran. A HBV mass vaccination schedule was launched in Iran in 1993. For this study, we enrolled 1120 cases younger than 24 years. ELISA was applied to evaluate the presence of HBsAg, anti-HBs and anti-HBc. HBV-DNA presence was determined in all HBsAg-negative cases using nested polymerase chain reaction. The prevalence of HBsAg, anti-HBc and anti-HBs was 0.1, 0.54 and 39.9% respectively. Out of 6 anti-HBc-positive individuals, 4 cases also had anti-HBs. One case revealed HBsAg co-existence and the other one showed isolated anti-HBc. HBV-DNA was not detected in HBsAg-negative specimens. A very low prevalence of HBsAg and isolated anti-HBc was observed and no occult HBV infection was detected. It seems that evasion mutants are not a potential threat for HBV universal immunization efficacy in the vaccinated population.