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Background: Currently, there is no cure for epidermolysis bullosa (EB) but few studies have explored the role of aminoglycosides in promoting collagen 7 expression in recessive dystrophic EB (RDEB). Materials and Methods: Consecutive patients aged >1 year with a confirmed diagnosis of dystrophic EB (DEB) were advised to apply 0.1% w/w gentamicin cream in a collagen base (Derbriment GTM) twice daily on a representative area on right lower limb (RLL) and paraffin gauze dressings on the corresponding opposite side on the left lower limb (LLL). Skin lesions were evaluated clinically during the 12-week treatment period at the end of which a repeat skin biopsy was sent for immunofluorescence antigen mapping (IFM). Results: Twelve patients with DEB were recruited but only eight completed the study and were analyzed. The mean fluorescence intensity (MFI) of the study cohort increased from 2765 ± 1732.07 (263–4845) at baseline to 5412.75 ± 3937.64 (2100–13536) at 12 weeks; a 95.75% (range 5.34%–775.14%) increase in the MFI of collagen 7 from baseline (P = 0.06). Among patients with a known termination codon mutation (n = 3), the percentage increase in MFI was greater among patients with known premature termination codon (PTC) mutations compared to those with unknown mutations. The clinical severity did not change significantly in terms of the mean number of blisters, erosions, and scarring during the study period. None of the parents reported any adverse effect. Conclusions: Topical gentamicin 0.1% w/w is a safe and effective way to promote the expression of COL7A1 in DEB patients, especially those carrying PTC mutations.

Introduction: Acquired dermal hyperpigmentation (ADMH) presenting on periorbital region has been described as individual case reports. We tried to characterize the features of periorbital ADMH. Materials and Methods: This was a retrospective case-control study among our patients who attended the pigmentary clinic during January 2016–December 2017. Clinical, dermoscopic, and histopathological features of subjects who were recruited during the study period were prospectively evaluated. Results: Total 19 subjects (11%) were identified among 177 ADMH patients. Periorbital ADMH patients had a relatively younger age of onset (23.26 ± 11.06 vs. 36.16 ± 13.41, P < 0.001). Dermoscopy of early periorbital ADMH showed only imperceptible speckled blue-gray dots that accentuated at outer-corner creases of eyes (the “outer-corner crease sign”). Clinicopathological features and prognosis of periorbital ADMH were similar to that of ADMH per se. Conclusion: Periorbital ADMH should be considered as a differential diagnosis of periorbital hyperpigmentation in children and young adults. Outer-corner crease sign on dermoscopy may help to rule out other differentials in its early presentation.

Context: Micropapillary variant of urothelial carcinoma (MPUC) is a rare but well-recognized tumor of the urinary bladder. Tumors with micropapillary areas accompanying conventional urothelial carcinoma are more aggressive compared to conventional urothelial carcinoma and show variable keratin 7, keratin 20 and human epidermal growth factor receptor 2 (Her 2)neu expression. Aim: The aim of the study was to analyze the clinical, morphological and immunohistochemical profile of MPUC. Materials and Methods: Transurethral resection of bladder tumor (TURBT) chips of seven cases of invasive MPUC with subsequent cystoprostatectomy specimens of five patients was reviewed. Epithelial membrane antigen (EMA), Keratin 7, Keratin 20, and Her 2 immunohistochemistry were performed in all cases. Follow-up information was available for all patients (2-36 months). Results: All seven patients were male, and their ages ranged from 50 to 62 years. All cases presented with hematuria. The micropapillary pattern was seen in 20-95% of the tumor. All cases showed extensive lymphatic emboli with detrusor muscle invasion. Lymph node metastasis was present in all cases undergoing cystoprostatectomy except one. Keratin 7 and abluminal pattern of EMA positivity were seen in all cases. Keratin 20 was positive in five cases (71%), and Her 2neu positivity was seen in four cases. Three patients died 2, 3, and 6 months after initial diagnosis, among which two were Her 2 positive and one was Her 2 negative. There was no clear prognostic significance of Her 2 positivity. Conclusion: (1) MPUC is a rare but highly aggressive tumor. (2) Micropapillary is usually the predominant pattern. (3) Keratin 7 is expressed universally, whereas Keratin 20 expression is variable. (4) Her 2 expression has no clear influence on the survival.

Sarcina is a Gram-positive anaerobic organism, having exclusively fermentative metabolism and has been associated with gastric outlet obstruction. We demonstrate the present case to highlight the presence of Sarcina with a coexisting gastric adenocarcinoma diagnosed on fine needle aspiration cytology.

In this brief report, we have described a rare case of schwannoma of the parotid gland in a young female who presented to us with a 3 cm diameter parotid swelling. The fine-needle aspiration cytology showed small fascicles, clusters and discrete spindle-shaped cells with long wavy nuclei. The cytological diagnosis of schwannoma of the parotid gland was offered and later confirmed by excision and histopathology.

Purpose. To evaluate the tibial articular cartilage and histology of the posterior cruciate ligament (PCL) in osteoarthritic knees so as to determine predictors of PCL degeneration. Methods. 23 advanced osteoarthritic knees (mean patient age, 61 years) treated with total knee arthroplasty (TKA) were prospectively studied. The Knee Society Score was assessed. Osteoarthritic changes on radiographs were graded as mild, moderate, or severe. Tibial articular cartilage erosion was assessed. The appearance of both cruciate ligaments was classified as normal, abnormal (thinner and sclerotic), or ruptured. Both ligaments were examined histologically for degenerative changes. Each degenerative change of the PCL was graded by 2 histopathologists twice separately. Higher scores indicated more severe degeneration. Results. Of the 23 knees, the gross appearance of the anterior cruciate ligaments (ACLs) was normal in 6, abnormal in 11, and ruptured in 6. Histologically, the PCLs were normal in 4, minimally degenerated in 2, mildly in 8, moderately in 5, and severely in 4. The predominant degenerative change was the presence of loose fibrous tissue. ACL appearance correlated positively with PCL degeneration ( r =0.883, p=0.001). The mean Knee Society Score was 24 (range, 0–43), and the mean function score was 30 (range, 5–55). PCL degeneration correlated positively with the Knee Society Score ( r =0.565, p=0.02) but not with the function score ( r =0.061, p=0.447). Anteroposterior instability correlated positively with PCL degeneration ( r =0.691, p=0.01). Erosion in the lateral tibiofemoral compartment and ACL insufficiency were indicators of PCL degeneration (despite a normal appearance). Inter-observer reliability and intra-observer reproducibility were 0.82 and 0.87, respectively. Conclusion. The Knee Society Score, anteroposterior instability, ACL appearance, and erosion in the lateral tibiofemoral compartment are predictors of PCL degeneration and can help decide on the optimal type of TKA implant (PCL-retaining vs. PCL-sacrificing design).

IntroductionDiabetes is a potent risk factor for the activation of latent tuberculosis and worsens the tuberculosis (TB) treatment outcome. The major reason for mortality and morbidity in diabetic patients is due to their increased susceptibility to TB. Thus, the study was conducted to understand the crosstalk between M. tuberculosis and its host upon latent tuberculosis infection and under hyperglycemic conditions or diabetes.MethodsAn animal model was employed to study the relationship between latent tuberculosis and diabetes. BCG immunization was done in mice before infection with M. tuberculosis, and latency was confirmed by bacillary load, histopathological changes in the lungs and gene expression of hspX, tgs1, tgs3 and tgs5. Diabetes was then induced by a single high dose of streptozotocin (150 mg/kg body weight). Host factors, like various cytokines and MMPs (Matrix metalloproteinases), which play an important role in the containment of mycobacterial infection were studied in vivo and in vitro.ResultsA murine model of latent TB was developed, which was confirmed by CFU counts (200 mg/dl. An in vitro study employing a THP-1 macrophage model of latent and active tuberculosis under normal and high glucose conditions showed that dormant bacilli were better contained in the presence of 5.5 mM glucose concentration as compared with active bacilli. However, the killing and restriction efficiency of macrophages decreased, and CFU counts increased significantly with an increase in glucose concentration.DiscussionThe decreased levels of MCP-1, decreased expression of mmp-9, and increased expression of mmp-1 in the latent group at high glucose concentrations could explain the failure of granuloma formation at high glucose conditions.

Abstract Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.

Abstract The evidence of an association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Thus, the study aims to delineate the role of diabetes in activation of latent tuberculosis infection. Murine model of latent tuberculosis and diabetes was developed, bacillary load and gene expression of resuscitation promoting factors (rpfA-E) along with histopathological changes in the lungs and spleen were studied. Treatment for LTBI [Rifampicin (RIF) + Isoniazid (INH)] was also given to latently infected mice with or without diabetes for 4 weeks. Diabetes was found to activate latent tuberculosis as the colony forming unit (CFU) counts were observed to be > 104 in lungs and spleen. The gene expression of hspX was downregulated and that of rpfB and rpfD was observed to be upregulated in latently infected mice with diabetes compared to those without diabetes. However, no significant reduction in the CFU counts was observed after 4 weeks of treatment with RIF and INH. Diabetes helps in the progression of LTBI to active disease mainly through altered expression of resuscitation promoting factors rpfB and rpfD, which can serve as important targets to reduce the shared burden of tuberculosis and diabetes.