Ultrastructure abnormalities of collagen and elastin in Arab patients with arterial tortuosity syndrome.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disease characterized by elongation and tortuosity of the large- and medium-sized arteries. ATS patients display features that are also found in Ehlers-Danlos syndrome (EDS) patients. ATS is caused by pathogenic mutations in the SLC2A10 gene, which encodes for the glucose transporter, GLUT10. This study aimed at examining the ultrastructure of skin for abnormalities that can explain the loose skin and arterial phenotypes of Arab patients with the p.S81R mutation in SLC2A10. Forty-eight patients with SLC2A10 mutation were recruited for this study. Skin biopsy specimens from three children with ATS and a healthy child were examined by electron microscopy to determine the ultrastructure of collagen and elastin. Histopathologic staining of sections from tissue biopsy specimens was also performed. Large spaces were observed among the collagen fibrils in the skin biopsy specimens obtained from ATS patients, suggesting disorganization of the collagen structures. Furthermore, elastin fiber contents and their thickness are reduced in the skin. In small muscular arteries in the skin from ATS patients, discontinuous internal elastic lamina, lack of myofilaments, and disorganized medial smooth muscle cells with vacuolated cytoplasm are present. The disorganization of collagen fibrils and reduced elastin contents in the skin may explain the loose skin phenotype of ATS patients similar to the EDS patients. The lack of elastin in small muscular arteries may have contributed to the development of arterial tortuosity in these patients.

A case of dyschromatosis symmetrica hereditaria with an associated eyelid hemangioma.

INTRODUCTION AND IMPORTANCE: Dyschromatosis symmetrica hereditaria (DSH) are rare autosomal dominant pigmentary genodermatosis characterized by reticular hyper- and hypopigmented skin macules on the dorsal aspect of the extremities and freckle-like spots on the face, sparing the palms and soles. Cutaneous hemangiomas were not reported in the literature with DSH. We describe for the first time to the best of our knowledge a case of DSH with histopathologically confirmed eyelid hemangioma. CASE PRESENTATION: A 25-year-old female was diagnosed with DSH in her childhood by a dermatologist then later developed cutaneous lupus erythematosus (CLE). Four years later she presented to our clinic with right lower eyelid painless mass. The histopathological examination showed inflamed epidermis overlying a mixed capillary and cavernous hemangioma. The patient had complete healing of the skin post-operatively with excellent cosmetic result. DISCUSSION: DSH is usually isolated, however, acral hypertrophy, psoriasis, dental anomalies, aortic valve sclerosis, dystonia and intracranial hemangiomas have been reported in association with the disease. The types of the hemangiomas reported were not specified with lack of tissue diagnosis. Our case is unique because of the late occurrence of this eyelid skin hemangioma, the concomitant CLE, the history of hyperthyroidism, and the positive family history of consanguinity. CONCLUSION: The pathogenesis of DSH is not well understood, however the previously reported intracranial hemangiomas and the currently reported skin vascular lesion would raise the role of inheritance and variable expression of such an association especially with concomitant CLE. This may warrant further studies on the etiology of DSH.

Clinical characteristics and outcomes in patients with primary Sjogren's syndrome-associated interstitial lung disease.

BACKGROUND: Diagnosing primary Sjogren's syndrome (pSS)-associated interstitial lung disease (ILD) is complex and can be very challenging. In addition, information about the prognostic factors is limited. AIMS: We aimed to determine the clinical characteristics and prognostic factors that impact pSS-ILD survival. METHODS: This retrospective review included 84 consecutive patients diagnosed with pSS-ILD. The information analyzed included the clinical characteristics, laboratory findings, and physiological and hemodynamic data. Prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: The mean age was 60.5 years, and 61.9% were females. The mean time between the onset of symptoms and diagnosis was 21 months (range, 1-98 months). Minor salivary gland biopsy (MSGB) was positive for pSS in 92.3% of the cohort. Fifty percent of the patients had negative autoimmune serology related to pSS. Based on the available hemodynamic data, 40% had pulmonary hypertension (PH), and 20% had severe PH. During follow-up, acute exacerbation was noted in 38% of the cohort. The 5-year survival rate for all patients was 56%. Male sex, usual interstitial pneumonia pattern, and a reduced forced vital capacity were independent predictors of mortality in the pSS-ILD patients. CONCLUSIONS: A significant delay between the onset of symptoms and diagnosis was noted in our cohort. Importantly, our study highlights the importance of MSGB and emphasizes that clinicians should not rely solely on serological tests to diagnose pSS in ILD patients. The overall survival was poor, and more efforts are needed to diagnose pSS-ILD at an early stage and refer patients to experienced centers.

The effect of low versus high tidal volume ventilation on inflammatory markers in animal model undergoing lung ventilation: A prospective study.

BACKGROUND AND AIMS: Mechanical ventilation (MV) with high tidal volume (Vt.) may induce or aggravate lung injury in critically ill patients. It might also cause an overwhelming systemic inflammation leading to acute lung injury (ALI), diffuse alveolar damage (DAD) and multiple organ failure (MOF) with subsequent high mortality. The objective of this study was to compare the effects of different Vt. on the inflammatory markers of the broncho-alveolar lavage (BAL) fluid and lung biopsy in a group of animal model (Beagle dogs). METHODS: A two-phased prospective study involving 30 Beagle dogs (15 dogs/phase), each phase divided into three groups (each 5 dogs/group). In the first phase each group received MV with Vt. of 8 (low), 10 (normal, control group), and 12 (high) ml/kg body weight (b.w.) respectively. BAL fluid was obtained at the time of induction of anesthesia immediately following tracheal intubation and one hour later following MV to count the macrophages, neutrophils and lymphocytes. In the second phase of the experiment, in addition to obtaining (BAL) fluid similar to the phase one, mini thoracotomy and lung biopsy obtained from the upper lobe of the right lung at same timings for histopathological examination study. Mann-Whitney-Wilcoxon test was used for statistical analysis of the data obtained. RESULTS: BAL fluid analysis showed increase in the counts of macrophages and lymphocytes with Vt. of 12 ml/kg b.w. compared to the control group (10 ml/kg b.w.) (P < 0.05). in the second phase, similar findings obtained. The histopathological study of the lung tissue obtained in the second phase of the study from the group that received a high Vt. of 12 ml/kg b.w. showed significant inflammatory changes with presence of neutrophil infiltration and edema in the bronchial wall compared to the control group (10 ml/kg b.w.) (P < 0.05). CONCLUSIONS: The use of high Vt. in ventilated animal lung model may increase the risk of inflammation and subsequent damage in healthy lungs, these findings may help physicians to avoid using high Vt. in short-term mechanically ventilated patients in the operating room setting.

Clinical characteristics, comorbidities, and outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a common subtype of interstitial lung disease (ILD). Information about the associated comorbidities and predictors of survival among Saudi patients with IPF is limited. AIMS: The aim of the study was to determine the clinical characteristics, associated comorbidities, and prognostic factors that impact IPF survival. METHODS: Consecutive IPF patients diagnosed in our ILD center were included. The information analyzed included demographics, physiological parameters, and associated comorbidities, among others. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 212 patients with IPF were available for the analysis. The mean age was 66.4 years, and 70.8% were male. The mean time between the onset of symptoms and diagnosis was 11.6 months (range: 1-48 months). Common comorbid conditions noted in the IPF cohort included pulmonary hypertension (49.6%), diabetes mellitus (43.2%), hypertension (42.2%), osteoporosis (40.4%), and gastroesophageal reflux disease (32.1%). Acute exacerbation (AE) was noted in 21.2% of the IPF patients. AE, final saturation <85%, walking distance <300 m, and antifibrotic therapy were independent predictors of survival. CONCLUSIONS: In our IPF cohort, we found that there was a significant delay between the onset of symptoms and diagnosis. Moreover, we identified multiple comorbidities associated with IPF, which increases the burden on both IPF patients and clinicians. Importantly, AE and the use of antifibrotic therapy were independent predictors of survival. It is of paramount importance for clinicians to diagnose IPF at an early stage, refer patients to experienced centers, recognize comorbidities, and initiate antifibrotic therapy regardless of the underlying disease severity.

Primary extramedullary plasmacytoma of the eyelid conjunctiva - A case report and review of the literature.

Extramedullary plasmacytomas (EMPs) are uncommon plasma cell tumors that develop in soft tissue as isolated tumors without osseous involvement while secondary lesions are associated with systemic multiple myeloma (MM). Primary extramedullary lesions are most commonly found in upper respiratory tract, gastrointestinal tract and lymph nodes. They can be found either in patients with history of MM or preceding the manifestation of a systemic disease. Orbital manifestation of the lesion is rare but conjunctival involvement is very unusual. The reported cases in the English-written literature are only five cases. Herein, we report the sixth case of primary EMP in a middle-aged adult who presented with a lesion confined to the conjunctiva, unremarkable present and past medical history, and confirmed tissue diagnosis. In addition, a review and summary of the previously reported cases in the literature is presented. We aim to attract the attention of ophthalmic surgeons to consider plasmacytoma within the differential diagnosis of a conjunctival lesion.

Clinical significance of minor salivary gland biopsy in patients with idiopathic interstitial pneumonia.

BACKGROUND: Significant overlap may occur between idiopathic interstitial pneumonia (IIP) and connective tissue diseases (CTDs) that do not meet the established classification criteria for any known CTDs (i.e., occult CTD). Performing minor salivary gland biopsy (MSGB) to detect occult primary Sjogren's syndrome (pSS) in IIP patients is not well studied. METHODS: Consecutive IIP patients underwent MSGB to determine the prevalence of positive MSGB findings. Furthermore, we characterised the clinical, physiological and serological profiles of the MSGB-positive patients. Cox regression models were used to identify independent predictors of survival. RESULTS: The data of 155 patients with IIP were available for analysis. Sixty patients (38.7%) had positive MSGB findings. Of them, the mean age was 63.3 years, 51.6% were women, usual interstitial pneumonia (UIP) was the predominant pattern (63.3%), and seronegative antibodies (61.6%) were likely. Patients with positive MSGB findings had significantly greater survival than those with negative MSGB findings (p = 0.041). After stratifying the MSGB cohort based on the presence of a UIP pattern, no significant difference in survival was noted between those with positive MSGB-UIP pattern and those with a negative MSGB-UIP pattern (p = 0.231). Multivariate analysis on all UIP patients showed that higher forced vital capacity (p = 0.010) and smoking status (p = 0.035) were independently associated with survival. CONCLUSIONS: A substantial number of IIP patients had underlying occult CTD, highlighting the importance of performing MSGB to identify the salivary component of pSS when evaluating patients with interstitial lung disease of undetermined aetiology.

Linear dermatomyofibroma over the nape of neck: a report of an unusual case and literature review.

Dermatomyofibroma is a rare cutaneous mesenchymal tumor of benign fibroblastic and myofibroblastic derivations. It predominantly affects young women, and it usually presents as a reddish-brown plaque or nodule, which is commonly located over the upper trunk. We report the case of a 41-year-old female patient who presented with progressive linear dermatomyofibroma over the nape of her neck. This case report expands the knowledge about the clinical and histopathological features of this rare, benign and cutaneous tumor.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Unusual presentation.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNEC) is an abnormal proliferation of pulmonary neuroendocrine cells that occur without underlying etiology. Here, we report a unique case of 55-year-old female with unusual presentation of DIPNECH and thymoma and on the background history of Crohn's disease that might point toward an autoimmune phenomenon. To the best of our knowledge, there were no previous reports of DIPNECH with either thymoma or Crohn's disease. DIPNECH has premalignant potential and reported in association with carcinoid and non-small cell lung cancer; however, its autoimmune association never reported. The presence of multiple lung nodules along with evidence of small airway disease should alert the physician to include DIPNECH as part of the differential diagnosis given its malignant potential. The prognosis is variable and depends on the presence or absence of underlying malignancy as well as the severity of airflow obstruction.

Molecular subtypes of breast carcinoma in Saudi Arabia. A retrospective study.

OBJECTIVES: To determine the distribution of various molecular subtypes of breast cancer in Saudi Arabia and to assess the association between these subtypes and age at diagnosis, tumor size, histopathological type, grade, presence of carcinoma in-situ, and lymph node status.  METHODS: This observational retrospective study, between January 2010 and  December 2014, was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. We classified 359 breast cancers into 4 molecular subtypes, using immunohistochemistry: luminal A (estrogen receptor [ER], or progesterone receptor [PR] positive and human epidermal growth factor receptor 2 [HER2] negative), luminal B (ER and/or PR positive and HER2 positive), HER2-positive (ER and PR negative and HER2 positive), and triple negative (ER, PR, and HER2 negative). We evaluated the relationship between these subtypes and clinicopathological features using Chi square test.   RESULTS: The most prevalent subtype was luminal A (58.5%), followed in descending order of frequency by triple negative (14.8%), luminal B (14.5%), and HER2-positive (12.3%). The average age at diagnosis was 49.8 years, and average tumor size at diagnosis was 3.19 cm.   CONCLUSION: Luminal A tumor was the most common molecular subtype and HER2-positive was the least common. Most lobular carcinomas were luminal A tumors. Human epidermal growth factor receptor 2-positive and triple negative tumors had a higher histologic grade and a larger tumor size at diagnosis, and they were more common in women under 50 years. Carcinoma-in-situ was least common in triple negative tumors. We found no association between lymph node status and molecular subtypes.