Oral vitamin D versus acitretin in congenital non-syndromic ichthyosis: double blinded, randomized controlled trial.

BACKGROUND: Vitamin D has emerged as a promising treatment for congenital ichthyosis for which no comparative studies exist. METHODOLOGY: In this randomized, double-blinded study, patients with congenital ichthyosis received either Vitamin D 2000 IU/day (group A) or acitretin 0.5 mg/kg/day (group B) for 24 weeks. The primary outcome was improvement in the Visual Index for Ichthyosis Severity (VIIS) and Ichthyosis Area Severity Index (IASI). Secondary outcomes included Ichthyosis Quality of Life Index-32 (IQoL-32), mRNA expression of RORγt and IL-17 and adverse events. RESULTS: Twenty-four patients completed the study. Group A (n = 11) showed a significant decrease in VIIS (p = 0.023) and IASI (p = 0.026) at 12 but not 24 weeks. Group B (n = 13) showed a significant decrease in IASI at 24 weeks only (p = 0.016). The IQoL-32 improved over 24 weeks in both groups. A significant decrease in the mRNA expression of RORγt (p = 0.048) and IL-17 (p = 0.023) was seen only in group A. There was no significant difference between the two treatment arms in terms of VIIS, IASI and IQol-32 at 12 and 24 weeks. No serious adverse events were observed. CONCLUSION: Vitamin D maybe an alternative to acitretin in the treatment of congenital ichthyosis where it reduces the expression of RORγt and IL-17.

Immunological response and clinical profile in patients with recurrent dermatophytosis.

BACKGROUND: An alarming increase in the number of patients with chronic and recurrent dermatophytosis has invoked the need to study the immunological parameters of the host. OBJECTIVES: To evaluate delayed type of hypersensitivity (DTH) response and immediate hypersensitivity (IH) response by flow cytometry evaluation of immune cells from peripheral blood and intradermal trichophyton skin test in patients with recurrent dermatophytosis. METHODS: A hundred patients with recurrent dermatophytosis and 50 controls (healthy controls and acute dermatophytosis controls) were included. Relevant risk factors for recurrence were analysed, and serum IgE levels were estimated. Flow cytometry evaluation of immune cells in peripheral blood and intradermal trichophyton skin test was done. Dermatophyte pathogens were isolated, and antifungal susceptibility was performed. RESULTS: Trichophyton mentagrophytes complex (95.84%) and T. rubrum (4.16%) were isolated in culture. Serum IgE was elevated in 83.15% cases (p = .01). IFN-γ+ cells (p = .0501, p = .0001, p = .0014), Th1 cells (p = .1197, p = .0024, p = .0169), IL-17+ cells (p = .0127, p = .0006, p = .0007) and Th17 cells (p = .0634, p = .0001, p = .0054) were reduced, and IL-4+ cells (p = .0108, p = .0175, p = .0018) were increased in cases. Intradermal test demonstrated negative DTH response in all cases (p < .001, p < .001, p < .001), strongly positive IH response in 6%, and borderline positive IH response in 85% cases (p = .018, p < .001, p < .001). Topical corticosteroids application, undergarment types (tight fit), poor frequency of washing clothes, family history of tinea, sharing of towels were significant risk factors for recurrent dermatophytosis. CONCLUSIONS: Reduced IFN-γ+ , Th1, IL-17+ and Th17 cells population along with impaired DTH response by the intradermal test was observed in patients with recurrent dermatophytosis.

Clinical and molecular features of X-linked hyper IgM syndrome - An experience from North India.

X-linked hyper IgM Syndrome (XLHIGM), the most frequent form of the Hyper IgM syndromes is a primary immune deficiency resulting from a mutation in the CD40 ligand gene (CD40LG). We analyzed the clinical and laboratory features of ten patients with XLHIGM, who were diagnosed at a tertiary care hospital in North India. Most common infections were sinopulmonary infections (80%) and diarrhea (50%). Sclerosing cholangitis and necrotising fasciitis were noted in one patient each. Three novel mutations in CD40LG (c.429_429 delA, p. G144DfsX5; c.500 G > A, p.G167E and c.156 G > C, p.K52 N) were detected. In addition, we found one missense mutation, two splice site mutations and two large deletions, which have been previously reported. Four (4) patients had expired at the time of analysis. We report the first series of XLHIGM from North India where we have documented unique features such as pulmonary alveolar proteinosis and infections with Mycobacterium sp.

Accuracy of Patient-Specific, 3D-Printed Laminofacetal Based Trajectory-Guide for Pedicle Screw Placement in Subaxial Cervical and Thoracic Spine.

Background: Conventional methods of pedicle-screw placement have higher breach rates due to variations in pedicle trajectories. Objective: We studied the accuracy of patient-specific, three-dimensional (3D)-printed laminofacetal-based trajectory guide for pedicle-screw placement in the subaxial-cervical and thoracic spine. Materials and Methods: We enrolled 23 consecutive patients who underwent subaxial cervical and thoracic pedicle-screw instrumentation. They were divided into two groups: group A (cases without spinal deformity) and group B (cases with pre-existing spinal deformity). Patient-specific, 3D-printed laminofacetal-based trajectory guide for each instrumented level was designed. The accuracy of screw placement was assessed on postoperative computed tomography (CT) using the Gertzbein-Robbins grading. Results: A total of 194 pedicle screws (114 cervical and 80 thoracics) were placed using trajectory guides, of which 102 belonged to group B (34 cervical and 68 thoracics). Out of a total of 194 pedicle screws, 193 had clinically acceptable placement (grade A: 187; grade B: 6; and grade C: 1). In the cervical spine, 110 pedicle screws out of a total of 114 had grade A placement (grade B: 4). In the thoracic spine, 77 pedicle screws out of a total of 80 had grade A placement (grade B: 2; grade C: 1). Out of a total of 92 pedicle screws in group A, 90 had grade A placement, and the rest 2 had grade B breach. Similarly, 97 out of a total of 102 pedicle screws in group B were placed accurately, 4 had grade B and another had a grade C breach. Conclusions: Patient-specific, 3D-printed laminofacetal-based trajectory guide may help in accurate placement of subaxial cervical and thoracic pedicle screws. It may help reduce surgical time, blood loss, and radiation exposure.

Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape.

Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell cancer. This research aims to present a large database study highlighting the demographic, clinical, and pathological factors, racial disparities, prognosis, and survival of PRCC. The clinical and demographic data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and molecular data was cured from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. PRCC had a median age of diagnosis at 64 years, with a higher incidence in men (77%), and Whites (68%). 70.3% of cases were Grades I-IV (13, 53, 31, and 3%, respectively). In patients with known data, 85% were localized to the kidney, and 84% of cases were 7 cm in size. No metastasis occurred in 97% of the known data. The most common treatment offered was surgical resection (9%). The 5-year overall survival was 79%, with patients undergoing surgery having a 90.6% 5-year survival. Multivariable analysis revealed age > 60 years, Black race, poor histologic differentiation, distant metastases, and tumor size > 10 cm as independent risk factors for mortality. The most common mutations identified from the COSMIC database were MET, KMT2D, KMT2C, ARID1A, and SPEN. PRCC affects male individuals in the sixth decade of life. Increased age, Black race, distant metastases, and tumors > 10 cm are associated with a worse prognosis. Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches.

Clinical Profile of Hyper-IgE Syndrome in India.

Introduction: Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to Staphylococcal skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES. Materials and Methods: A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis. Results: Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%). Mycobacterial infections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12. Conclusions: The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant. Mycobacterial diseases were more frequent, compared to western literature.

Metabolic Syndrome and Its Effects on Cartilage Degeneration vs Regeneration: A Pilot Study Using Osteoarthritis Biomarkers.

BACKGROUND: Osteoarthritis (OA) of the knee is one of the leading causes of disability characterized by degeneration of hyaline cartilage combined with reparative processes. Its strong association with metabolic syndrome is postulated to be due to both mechanical and biochemical factors. Our study aims to study differential effect of metabolic risk factors on cartilage degeneration and regeneration at biomarker level. DESIGN: After screening 281 patients presenting with knee pain, 41 patients who met the selection criteria were included and were divided into metabolic (MetS) OA and non-metabolic (Non-MetS) OA phenotypes using National Cholesterol Education Programme-Adult Treatment Panel-III (NCEP-ATP-III) criteria for metabolic syndrome. Serum Cartilage Oligomeric Matrix Protein (COMP) and Procollagen type IIA N terminal Propeptide (PIIANP) levels were used as tools to assess cartilage degeneration and regeneration, respectively. RESULTS: 22 among 41 patients (53.66%) had metabolic syndrome. Covariates like age, gender, Kellgren Lawrence (KL) grades were comparable in both groups. MetS-OA group showed significant increase in serum COMP levels (p = 0.03) with no significant effect on serum PIIANP levels (p = 0.46). Hypertriglyceridemia showed independent association with both cartilage anabolism (p = 0.03) and catabolism (p = 0.03). CONCLUSION: Metabolic syndrome, though has no effect on cartilage regeneration tends to shift cartilage homeostasis towards degeneration with hypertriglyceridemia showing significant independent effect on cartilage metabolism.

Metabolic syndrome and female gender, but not methotrexate, are the important associations of significant liver fibrosis in patients with moderate-to-severe psoriasis as detected by transient elastography.

BACKGROUND: Many international guidelines on psoriasis management have emphasized upon the need to identify risk factors for liver fibrosis and that the risk may be increased after a certain total cumulative dose of methotrexate. METHODS: Consecutive patients with moderate-to-severe psoriasis were assessed for liver fibrosis using transient elastography and noninvasive scores. Based on the presence of significant liver fibrosis, the Odds ratio associated with various factors was calculated using logistic regression analysis. Receiver operating characteristic curves were calculated to find maximal cutoff values of noninvasive tests to detect fibrosis. RESULTS: In this cross-sectional study, 134 patients completed the study. Significant fibrosis (liver stiffness measurement ≥7, corresponding to F2 fibrosis or higher) was seen in 33 (24.6%) patients. Neither methotrexate exposure nor total cumulative dose of ≥1.5 was associated with significant fibrosis. Female sex (P = 0.024) and the presence of metabolic syndrome (P = 0.034) were the two variables associated with significant liver fibrosis. On logistic regression analysis, the odds ratio for the female gender and metabolic syndrome was estimated to be 2.51 (95% confidence interval - 1.09-5.81) and 2.33 (95% confidence interval - 1.03-5.27), respectively. Aspartate transaminase to platelet ratio index, nonalcoholic fatty liver disease score and the fibrosis-4 index had low sensitivity in comparison to transient elastography. LIMITATIONS: These included small sample size, small number of patients with a total cumulative methotrexate dose of >3-4.5 g, and lack of control group consisting of healthy persons. Another is the absence of liver biopsies considered as the gold standard in the diagnosis of liver fibrosis. CONCLUSIONS: Metabolic syndrome and female sex are associated with the development of significant liver fibrosis in patients with psoriasis. Methotrexate exposure does not seem to be significantly associated with significant liver fibrosis.

A unilateral purple urine bag syndrome in a patient with bilateral nephrostomy tubes.

A change in the colour of urine is always of clinical significance, and a source of concern for the patient and his physician. Among the different urine colours observed, purple is the least common. Although purple discolouration of a catheter and a urine bag is an uncommon finding, it was reported in the literature as early as 1978, by Barlow and Dickson. We present a unique case of purple urine bag syndrome in a patient with bilateral nephrostomy tubes (NT) and associated urine bags (UB) with only the left nephrostomy tube and urine bag exhibiting the purple colour, which resolved with a course of appropriate antibiotics eradicating the causative bacterial pathogen, and change of NT and UB.

Statin use is not associated with presence of and severity of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: There is concern that statin use may exacerbate nonalcoholic fatty liver disease (NAFLD). We aimed to assess the association of statin use with NALFD and severity of liver fibrosis among NAFLD individuals. METHODS: We evaluated 6,385 cross-sectional healthy Brazilian subjects (43 ± 10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. NAFLD was diagnosed by ultrasound. Severity of liver fibrosis was predicted by fatty liver index and FIB-4. RESULTS: NAFLD prevalence was 36% (n = 2310). Overall 552 (9%) individuals were using statins of whom 49% had NAFLD. Statin users were more likely to be men, older age, and have higher burden of risk factors (p <0.05). In age gender adjusted analysis the odds ratio for NAFLD with statin use was 0.87 (0.61-1.25, p = 0.46) in the presence of metabolic syndrome and 1.08 (0.88-1.32, p = 0.56) in its absence. On further adjustment for metabolic risk factors, LDL and smoking the results remained unchanged (OR: 0.89, 95% CI: 0.65-1.32, p = 0.56 and 0.90 (0.69-1.18, p = 0.46). There was no significant association between statin use and fatty liver index in a subanalysis of NAFLD individuals (71 ± 18 vs. 69 ± 23, p = 0.18). Although FIB-4 was mildly elevated with statin use (1.20 ± 0.51 vs. 1.02 ± 0.46, p <0.001), a multivariate analysis adjusted for age, gender and risk factors revealed statin use was not associated with severe fibrosis (FIB >1.45) (OR 0.88, 95% CI: 0.60-1.29, p = 0.50). CONCLUSIONS: The results of this study favor statin use in subjects with NAFLD as its use is not associated with the presence of NAFLD or increased fibrosis.

Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

Subclinical cardiovascular disease in plaque psoriasis: association or causal link?

BACKGROUND: Psoriasis patients have a high prevalence of cardiovascular events and are thought to have a relative risk increase of 25% as compared to the general population. However, a causal relationship between psoriasis and cardiovascular disease has not been established. We sought to perform a systematic review of existing data regarding the presence of endothelial dysfunction and subclinical atherosclerosis in patients with plaque psoriasis. METHODS: A systematic literature search was performed, using Medline database and Ovid SP for relevant literature up to November 2012. Twelve studies met inclusion criteria from an initial search result of 529 articles. RESULTS: Among the twelve studies meeting inclusion criteria, two (17%) reported increased mean coronary artery calcification (CAC) in psoriatic patients. Six studies (50%) showed carotid intima-media thickness [CIMT] increase in psoriasis. Five studies (42%) examined flow mediated dilation [FMD], of which three showed decreased FMD in psoriasis patients. One study (8%) each demonstrated a decreased coronary flow reserve and increased arterial stiffness as assessed by pulse wave velocity. CONCLUSIONS: Patients with psoriasis have an increased burden of subclinical atherosclerosis and endothelial dysfunction. Patients with greater severity and/or disease duration should be targeted for primary screening for cardiovascular disease risk reduction.

Late presentation of esophageal cancer: observations in a multiracial South-East Asian population.

OBJECTIVE: Esophageal cancer (ECA) is an important cancer in Malaysia. The aim of the study is to review the demographic data and clinical presentation of patients with ECA seen at the University of Malaya Medical Centre, Kuala Lumpur. METHODS: Patients with histologically proven ECA were recruited for the study. Patients' case notes, endoscopy and operating theater records were reviewed. All cases were histologically confirmed. RESULTS: A total of 143 patients with ECA was diagnosed between 1998 and 2003. The mean age of the patients was 63.1 +/- 12.1 years with a male : female ratio of 1.8:1. Of these 50.3 percent were Indians, 32.9 percent, Chinese and 16.8 percent Malays. The overall hospital-based prevalence rates per 100 000 admissions according to races were: Malay; 23.5, Chinese; 57.4 and Indian; 134.1. The location of the tumors was: upper; 16 (11.2%) middle; 52 (36.4%) and lower; 75 (52.4%). The histological type of ECA were: squamous cell carcinomas; 113 (79.0%) and adenocarcinomas; 30 (21.0%). The ECA stage at diagnosis, was: II; 18 (12.6%), III; 23 (16.1%) and IV; 102 (71.3%). Only 24 (16.8%) patients underwent surgery and13 (9.1%) were considered curative. Overall 114 (79.7%) patients underwent palliative endoscopic stenting and six (4.2%) were given other palliative therapy including radiotherapy. CONCLUSIONS: Squamous cell cancer was the predominant type. ECA presents late in our patients and only a minority of patients underwent curative surgery.