Mast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFß-dependent manner.

Mast-cell expressed membrane protein-1 (MCEMP1) is higher in patients with idiopathic pulmonary fibrosis (IPF) with an increased risk of death. Here we aimed to establish the mechanistic role of MCEMP1 in pulmonary fibrosis. We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared with controls. MCEMP1 is upregulated by transforming growth factor beta (TGFß) at the mRNA and protein levels in monocytic leukemia THP-1 cells. TGFß-mediated MCEMP1 upregulation results from the cooperation of SMAD3 and SP1 via concomitant binding to SMAD3/SP1 cis-regulatory elements within the MCEMP1 promoter. We also found that MCEMP1 regulates TGFß-mediated monocyte chemotaxis, adhesion, and migration. Our results suggest that MCEMP1 may regulate the migration and transition of monocytes to monocyte-derived alveolar macrophages during pulmonary fibrosis development and progression.NEW & NOTEWORTHY MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages in IPF, is regulated by TGFß, and participates in the chemotaxis, adhesion, and migration of circulating monocytes by modulating the effect of TGFß in RHO activity.

Sarcoidosis-associated pulmonary fibrosis: joining the dots.

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis (SAPF), which may become progressive. Genetic profiles differ between patients with progressive and self-limiting disease. The mechanisms of fibrosis in SAPF are not fully understood, but SAPF is likely a distinct clinicopathological entity, rather than a continuum of acute inflammatory sarcoidosis. Risk factors for the development of SAPF have been identified; however, at present, it is not possible to make a robust prediction of risk for an individual patient. The bulk of fibrotic abnormalities in SAPF are located in the upper and middle zones of the lungs. A greater extent of SAPF on imaging is associated with a worse prognosis. Patients with SAPF are typically treated with corticosteroids, second-line agents such as methotrexate or azathioprine, or third-line agents such as tumour necrosis factor inhibitors. The antifibrotic drug nintedanib is an approved treatment for slowing the decline in lung function in patients with progressive fibrosing interstitial lung diseases, but more evidence is needed to assess its efficacy in SAPF. The management of patients with SAPF should include the identification and treatment of complications such as bronchiectasis and pulmonary hypertension. Further research is needed into the mechanisms underlying SAPF and biomarkers that predict its clinical course.

Dermatological adverse drug reactions to tyrosine kinase inhibitors: a narrative review.

Tyrosine kinase inhibitors (TKIs) target the signal transduction pathways of protein kinases by several modes of inhibition. Adverse effects are generally dose dependent, with certain side-effects unique to each drug. However, due to similarities in target sites, different classes of TKIs may have identical or overlapping side-effect profiles. This narrative review is an attempt to summarize the common and uncommon adverse effects of different classes of TKIs.

Comparison of Effectiveness and Safety of Immunotherapy of Warts with Intralesional Versus Subcutaneous MMR Vaccine: An Open Label Randomized, Parallel Group, Clinical Trial.

Common wart, also known as verruca vulgaris is characterized by focal proliferation of keratinocytes caused by multiple strains of human papilloma virus (HPV). Conventional treatments like chemical cautery, cryotherapy, electro-cautery, etc often fail to cure verruca satisfactorily. The present work was a randomized, parallel-group, non-inferiority clinical trial with an objective of comparing the effectiveness and safety of subcutaneous MMR versus intralesional MMR vaccine in the treatment of multiple warts. Method: Consenting patients of both sexes of 18-65 years age, who have viral warts and did not receive anti-wart treatment in the last 4 weeks and devoid of any active bacterial or viral skin diseases were included in the study. Interventions: Eligible patients were randomized into either group A (receiving 0.3 ml of intralesional MMR) or group B (receiving 0.5 ml of subcutaneous MMR). A total of three injections were administered at two weeks interval. Outcome Measure: The response was considered complete if there was disappearance of the wart(s) and return of the normal skin markings, partial if the wart(s) was regression in size by 50-99% and no response if there was be 0-49% decrease in wart size. Results: Thirty patients were recruited in each group; 5 of group A and 3 of group B were lost to follow up. Modified intention to treat analysis was performed, so, the last observation of such patients was carried forward and all 60 participants were analysed. Number of warts and size of the largest wart were declined significantly (P < 0.001 and P = 0.001 respectively) in both the treatment arms. No significant difference between two groups were seen. Complete clearance including distant lesions was achieved in 22 patients; 12 (48%) in group A and 10 (37.04%) in group B, but the final outcome at the end of the study showed no significant difference between the two t groups. (P = 0.64). Adverse Events: Only one patient had developed mild fever with tender, enlarged parotid gland after first injection of subcutaneous MMR which resolved within two weeks. Conclusion: Efficacy and safety profile of Subcutaneous and intralesional MMR were almost same. Both can be considered as safe and cost effective treatment of warts while the subcutaneous route may be easier to administer.

Perioperative approach to precapillary pulmonary hypertension in non-cardiac non-obstetric surgery.

Pulmonary hypertension (PH) confers a significant challenge in perioperative care. It is associated with substantial morbidity and mortality. A considerable amount of information about management of patients with PH has emerged over the past decade. However, there is still a paucity of information to guide perioperative evaluation and management of these patients. Yet, a satisfactory outcome is feasible by focusing on elaborate disease-adapted anaesthetic management of this complex disease with a multidisciplinary approach. The cornerstone of the peri-anaesthetic management of patients with PH is preservation of right ventricular (RV) function with attention on maintaining RV preload, contractility and limiting increase in RV afterload at each stage of the patient's perioperative care. Pre-anaesthetic evaluation, choice of anaesthetic agents, proper fluid management, appropriate ventilation, correction of hypoxia, hypercarbia, acid-base balance and pain control are paramount in this regard. Essentially, the perioperative management of PH patients is intricate and multifaceted. Unfortunately, a comprehensive evidence-based guideline is lacking to navigate us through this complex process. We conducted a literature review on patients with PH with a focus on the perioperative evaluation and suggest management algorithms for these patients during non-cardiac, non-obstetric surgery.

Dermatoses in the Elderly: Clinico-Demographic Profile of Patients Attending a Tertiary Care Centre.

BACKGROUND: Elderly population is vulnerable to develop a multitude of dermatological diseases, owing to comorbidities and polypharmacies. OBJECTIVE: To know the prevalence of dermatological conditions in elderly patients attending outpatient department, determine the pattern and relative frequency of skin diseases, and find the relation with associated comorbidities. MATERIALS AND METHODS: We performed a cross-sectional study on 250 patients, aged ≥60 years. Clinical diagnosis was done, followed by appropriate investigations when required. Descriptive data was analyzed on the parameters of range, mean ± S.D., frequencies, etc., Continuous variables were analyzed using unpaired t-test/Mann-Whitney U test and categorical data by Fisher's exact test/Chi-square test. Statistical software Medcalc version 10.2.0.0 for Windows vista was used. P value =0.05 was considered statistically significant. RESULTS: 250 patients were evaluated, 164 males (65.5%) and 86 females (34.4%). Mean age was 67.87 ± 7.29 years. Commonest disease category was infection (30%), followed by dermatitis (29.6%), papulo-squamous (18.4%), and immunobullous (6.4%). Difference in acute and chronic disease was significant (P = 0.0001). 30% had infections; fungal (50.66%), bacterial (32%), and viral (17.33%). 74 patients had dermatitis (29.6% of study population). Commonest systemic disease was hypertension (23.2%), followed by diabetes mellitus (19.6%). Association of diabetes mellitus was significant (P = 0.0014), more in infective dermatoses (P = 0.0007). All had signs of aging; idiopathic guttate hypomelanosis (51.2%), xerosis (45.2%), seborrheic keratosis (42.6%), cherry angioma (33.2%), senile acne (6.6%). Photoaging was noted as wrinkling (98.8%), freckles (35.6%), purpura (10.8%), telangiectasia (5.6%). People involved in outdoor activity had higher Glogau scale (3.01 ± 0.69) compared to those indoors (2.44 ± 0.74), statistically significant difference (P = 0.001). CONCLUSION: Our study is the first of its kind, in Eastern India, where we evaluated and explored the disease pattern and extent of geriatric dermatoses among patients attending dermatology OPD of a tertiary care hospital.

Phakomatosis Pigmentovascularis: A Clinical Profile of 11 Indian Patients.

INTRODUCTION: Phakomatosis pigmentovascularis (PPV) is a rare congenital syndrome characterized by the simultaneous presence of capillary malformation and pigmentary nevi. The objective of our study was to describe the clinical characteristics of a series of Indian patients presenting with this rare entity. MATERIALS AND METHODS: It was a record-based descriptive case series. RESULTS: A total of 11 patients with PPV (9 females, 2 males, age range: 7 days to 45 years; mean 11.6 years) were studied. Port wine stain was present in 10 (91%) patients and one patient (9%) had cutis marmorata telangiectatica congenita. Isolated nevi of Ota and Mongolian spots were seen in 4 (36%) patients each. Simultaneous presence of both Mongolian spots and nevus of Ota was present in 1 (9%) patient. The combination of Mongolian spots and bilateral palatal hyper-melanosis was noticed in 2 (18%) patients. Café au lait macule was present in one patient. Bilateral ocular melanosis was found in 3 (27%) patients. Unilateral ocular melanosis was noticed in 4 (36%) patients. Two patients (18%) had history of seizure disorder and intracranial vascular anomalies on MRI imaging. Two patients (18%) had features of Klippel-Trenaunay syndrome. According to the traditional classification, three patients had PPV type 2b, one patient had PPV type 5b, and seven patients had PPV type 2a. According to the Happle's classification, 10 patients had PPV of cesio flammea type, and one patient had PPV of cesio marmorata type. LIMITATIONS: We could not perform genetic study of the patients. CONCLUSION: Our findings emphasize the importance of detailed systemic evaluation including ocular examination and brain imaging in every patient of PPV.

Dermatopathia Pigmentosa Reticularis.

Dermatopathia pigmentosa reticularis is a rare ectodermal dysplasia that presents with a triad of reticulate hyperpigmentation, nonscarring alopecia, and nail dystrophy. We report herein a case of a 23-year-old male presenting with the characteristic triad associated with anhidrosis and palmoplantar keratoderma.

A single-institution study of concordance of pathological diagnoses for interstitial lung diseases between pre-transplantation surgical lung biopsies and lung explants.

BACKGROUND: By comparing diagnoses made by pre-transplant surgical lung biopsy (SLB) and the final pathologic diagnosis of the explanted pathology (EP), we aimed to study the factors that could impact pathologic diagnoses in patients with interstitial lung disease (ILD). METHODS: We retrospectively reviewed the lung transplant database at Cleveland Clinic [01/01/2006-12/31/2013] to include all lung transplant recipients with a prior diagnosis of ILD. Two pulmonary pathologists independently reviewed each SLB and lung explant. The diagnoses were labeled as concordant (same diagnosis on SLB and explant) or discordant (diagnosis on SLB and explant were different) by consensus. RESULTS: Of 389 patients transplanted for ILD, 217 had an SLB before transplant. Pathological diagnoses were concordant in 190 patients (87.6%) [165 UIP (86.8%), 13 NSIP (6.8%), 8 CHP (4.2%) and 4 other diagnoses (2.1%). In 27 cases (12.4%), the diagnosis on SLB differed from EP. 8/27 were diagnosed with UIP on SLB and of these, 5 were re-classified as NSIP. 14/19 (73.7%) patients with a SLB diagnosis "other than UIP" were re-categorized as UIP based on explant. Discordant cases had a greater time between SLB and EP than concordant cases (1553 days vs 1248 days). CONCLUSIONS: The pathologic diagnosis of ILD by SLB prior to lung transplant is accurate in most patients, but may be misleading in a small subset of patients. The majority of discordant cases that were reclassified as UIP could be due to a sampling error, or perhaps, an increased time from the date of the SLB to transplant. Future studies examining how multidisciplinary consensus diagnosis affects this discordance are necessary.

The color of skin: green diseases of the skin, nails, and mucosa.

Greenish staining of human skin may result from a gamut of causes, such as chlorosis, exogenous copper, resolving ecchymosis, drugs, green textile dyes, green tattoos, apocrine and eccrine chromhidrosis, hyper biliverdinemia, chloromas, use of green dyes during tube feeding in patient with multiorgan failure, Pseudomonas infections, and Wells' syndrome in its second stage. Physicians may rarely encounter patients with green skin, hair, nails, or mucosae.

Intraluminal Arterial Filling Defects Misdiagnosed as Pulmonary Emboli: What Else Could They Be?

Pulmonary artery filling defects can be observed in various pathologic processes other than pulmonary embolism, for example, nonthrombotic pulmonary embolism with biological and nonbiological materials and intrinsic pulmonary artery lesions. They have also been described in rare conditions, such as fibrosing mediastinitis and congenital absence or stenosis of pulmonary artery, and some pulmonary parenchymal and airway malignancies. Misdiagnosis is common owing to the relative rarity of these conditions. Correct diagnosis is based on the appropriate clinical suspicion considering the unique clinical features, laboratory findings, and additional radiologic clues inferring a pathology other than pulmonary embolism.

Clinical and Histopathological Response to Multidrug Therapy in Paucibacillary Leprosy at the end of 6 Months: A Prospective Observational Study from Eastern India.

BACKGROUND: At present, the WHO recommends fixed duration multidrug therapy (FD-MDT) for the treatment of leprosy, in which treatment is provided for a fixed duration regardless of clearance of skin lesions or bacterial status of the patient. There is divided opinion regarding the efficacy of FD-MDT; especially for paucibacillary Hansen's disease, in which treatment is provided for 6 months. In addition, there is a paucity of literature on clinical and histopathological features of treated leprosy. OBJECTIVES: The objectives of this study were to prospectively observe the effects of MDT on clinical and histopathological features in paucibacillary leprosy and to assess the efficacy, safety and tolerability of MDT-paucibacillary (PB) regimen. MATERIALS AND METHODS: A total of 52 new cases of PB leprosy diagnosed by clinicopathological correlation and slit skin smear were administered standard WHO PB-MDT for 6 months. Patients were reviewed at 3rd month and 6th month of therapy and 3 months posttherapy for their clinical and histopathological assessment. RESULTS: Among 52 new cases of PB-leprosy 43 patients (mean age 31.74 ± 12.2 years, m:f 1.53:1) completed the study as per protocol. Fourteen percent patients recovered completely, 76.7% patients had a residual patch at the end. Number of lesions reduced significantly 2nd follow-up onwards while the lesional size showed significant decrease 1st follow-up onward. Nerve palpability also reduced significantly at treatment completion. Histological improvement was appreciable; lymphocytic infiltration reduced significantly 2nd follow-up onward and presence of granuloma 1st FU onward. Only four patients complained of occasional, uneventful epigastric pain during the study. CONCLUSION: Although the frequency of persistence of lesions after completion of therapy was high, histological evidence of activity was present in a minority (7%). Thus, the standard WHO MDT-PB regimen was found to be effective, safe and well-tolerated.

Usefulness and Utility of NACO Regime in the Management of Sexually Transmitted Infections: A Pilot Study.

INTRODUCTION: Treatment of sexually transmitted infections (STIs) has been made easy for field workers due to syndromic approach. The etiological agent responsible for different STI syndromes needs to be validated from time to time so as to guide the therapeutic regimen. AIMS AND OBJECTIVES: The aim of this study was to evaluate the etiological agent for STI syndromes and correlate the syndromic diagnosis with etiological diagnosis. MATERIALS AND METHODS: The study was conducted over 9 months in all patients attending the STI and Gynaecology Outpatient Department. Syndromic diagnosis was done by STI-trained medical officer of respective clinic. Sample was collected for etiological diagnosis and subjected to relevant investigations. Data were analyzed by applying statistical methods. RESULTS: Among 308 patients (male:female = 1:3.5), no syndromic diagnosis could be made in 11 cases (all females and had premalignant changes on Pap smear). In 68 patients (22.08%), no etiological diagnosis could be arrived at (mostly genital ulcer disease [GUD]-herpetic [H] and vaginal discharge). In cervical discharge syndrome, six patients (16.7%) showed gonococcus. In GUD-H syndrome, 37 patients (27.027%) were tested positive. In GUD-nonherpetic syndrome, three patients (33.33%) were syphilis, granuloma inguinale, and chancroid (1 each). In urethral discharge syndrome, etiology could not be found in 33 cases (45.45%). In vaginal discharge syndrome (n = 217), etiologies were overlapping as follows: trichomonas vaginalis (76.04%), bacterial vaginosis (40%), gonococcus (24%), and undiagnosed (6.5%). CONCLUSION: The present tool for validation of GUD-H can validate only 27% of cases. Overlap of etiologies is mostly common in vaginal discharge syndrome, wherein malignancies and premalignant conditions are overtreated with kits. Validation can be done only in two-third of cases with the available resources. However, syndromic approach provides the opportunity of treating STI without delay.

Primary pulmonary artery sarcoma: a close associate of pulmonary embolism-20-year observational analysis.

BACKGROUND: Primary pulmonary artery sarcoma (PPAS) is a rare tumor that mimics pulmonary thromboembolism (PE). Similarities to PE can delay the diagnosis and misguide the treatment of PPAS. This study aimed to evaluate tumor characteristics and outcome predictors among those diagnosed with PPAS and misdiagnosed as PE. METHODS: From 1991-2010, 10 PPAS cases were available from the Cleveland Clinic (CC) institutional database and another 381 cases were reported in the literature. Patient characteristics, tumor subtypes, diagnostic testing & timing, interventions and clinical outcomes were analyzed. We also noted effects of misdiagnosis as PE and clinical outcome as a result of inappropriate intervention. RESULTS: Among 391 confirmed cases of PPAS, the mean age at diagnosis was 52±14 years; 55% were male. The median duration of symptoms prior to diagnosis was 100 [interquartile range (IQR), 30-210] days. Nearly half (47%) of PPAS were originally misdiagnosed as PE including 39% that received thrombolytic and/or anticoagulation therapy. For every doubling of time from symptom onset to diagnosis, the odds of death increased by 46% (OR: 1.46, 95% CI: 1.21-1.82; P<0.001). The odds of death (OR: 2.66, 95% CI: 1.58-4.54; P=0.0003) and occurrence of distant metastasis (OR: 2.30, 95% CI: 1.30-4.15; P=0.049) were increased among those who did not receive chemotherapy but chemotherapy did not impact local recurrence. Those with complete resection had a better survival. CONCLUSIONS: PPAS has a radiological appearance similar to PE, which makes accurate and timely diagnosis challenging. More rapid diagnosis may lead to earlier, appropriate surgical treatment and improved outcomes, when combined with adjuvant treatment.

Plugs of the Air Passages: A Clinicopathologic Review.

Although mucus is a normal product of the tracheobronchial tree, some diseases of the respiratory tract are characterized by unusually thick (inspissated) forms of mucus that accumulate within the airways. These are known as mucus plugs. The pathologic composition of these plugs is surprisingly diverse and, in many cases, correlates with distinctive clinical, radiologic, and bronchoscopic findings. The best-known conditions that involve mucus plugs are allergic bronchopulmonary aspergillosis, plastic bronchitis, and asthma. Other lung diseases occasionally associated with plugs within the airways include Aspergillus tracheobronchitis, hyper-IgE syndrome, exogenous lipoid pneumonia, pulmonary alveolar proteinosis, and chronic eosinophilic pneumonia. In this review, we describe and illustrate the bronchoscopic, pathologic, and imaging findings in respiratory disorders characterized by mucus plugs or plugs composed of other similar materials. Recognition of the characteristic appearance and differential diagnosis of mucus plugs will hopefully facilitate diagnosis and management of these diseases.

A Weeping Tumor in a Young Girl: An Unusual Presentation of Nodular Hidradenoma.

A 10-year-old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion. Based on histological features of the excised tumor, a diagnosis of nodular hidradenoma was made. Atypical features including large size of the tumor, location on the lower limb, a weeping presentation, and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case.

Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation.