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Introduction: Left atrial appendage occlusion (LAAO) is recommended in patients with non-valvular atrial fibrillation (AF) who have contraindications to or are intolerant of long-term oral anticoagulants (OAC), but its impact on hospitalization rates has not been well described. The objective of our study is to describe the incidence of all-cause, bleeding-related, and thrombosis-related hospitalizations before and after LAAO., Material and Methods: We used the Nationwide Readmission Database to include patients aged ≥ 18 years with a diagnosis of AF who underwent transcatheter LAAO during the months of February-November in each year between 2016 and 2018. Patients who died during the index procedure or had missing length of hospital stay or mortality information were excluded., Results: A total of 27,633 patients were included (median age: 77 years, 41% female) with an average pre- and post-LAAO monitoring period of 6.5 and 5.5 months respectively. Of these, 10,808 (39.1%) patients had one or more admissions prior to the procedure compared to 7,196 (26.0%) after the procedure. There was a 26% reduction in incidence of all-cause admissions (rate ratio (RR) = 0.74, 95% confidence interval (CI): 0.71-0.76; p < 0.001), 49% reduction in bleeding-related admissions (RR = 0.51, 95% CI: 0.48-0.55; p < 0.001), and 71% reduction in thrombosis-related readmissions (RR = 0.29, 95% CI: 0.26-0.33; p < 0.001) after LAAO., Conclusions: In a contemporary, nationally representative dataset, we found that LAAO is associated with a significant decrease in all-cause, bleeding-related, and thrombosis-related admissions. These findings lend support to the current use of transcatheter LAAO in clinical practice for patients with contraindications to OAC and/or at high risk of bleeding., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

Optical coherence tomography (OCT) provides excellent image resolution, however OCT optimal acquisition is essential but could be challenging owing to several factors. We sought to assess the quality of OCT pullbacks and identify the causes of suboptimal image acquisition. We evaluated 784 (404 pre-PCI; 380 post-PCI) coronary pullbacks from an anonymized OCT database from our Cardiovascular Imaging Core Laboratory. Imaging of the region-of-interest (ROI-lesion or stented segment plus references) was incomplete in 16.1% pullbacks, caused by pullback starting too proximal (63.7%), inappropriate pullback length (17.1%) and pullback starting too distal (11.4%). The quality of image acquisition was excellent in 36.3% pullbacks; whereas 4% pullbacks were unanalyzable. Pullback quality was most commonly affected by poor blood displacement from inadequate contrast volume (27.4%) or flow (25.6%), followed by artifacts (24.1%). Acquisition mode was 'High-Resolution' (54 mm) in 74.4% and 'Survey' (75 mm) in 25.6% of cases. The 54 mm mode was associated with incomplete ROI imaging (p = 0.020) and inadequate contrast volume (p = 0.035). We observed a substantial frequency of suboptimal image acquisition and identified its causes, most of which can be addressed with minor modifications during the procedure, ultimately improving patient outcomes.

Background: Vessel Fractional Flow Reserve (vFFR), a new angiography-derived method for the functional assessment of coronaries, was recently shown to have good correlation with invasive wire-derived FFR, when vFFR-specific image acquisition requirements were followed. We sought to investigate the feasibility of vFFR analysis and its correlation with FFR in the situation where angiography is completed in routine fashion, without intention for virtual analysis., Methods: Utilizing an anonymized database maintained at our Cardiovascular Imaging Core Laboratory, we included angiographic images from patients that underwent pre- and post-PCI FFR. CAAS Workstation 8.1 software (Pie Medical Imaging) was used for vFFR evaluation., Results: Out of 624 angiograms (312 pre-PCI and 312 post-PCI), vFFR was successfully analyzed in 219 (35.1%) (115 pre-PCI and 104 post-PCI). Reasons for vFFR analysis failure were: <2 angiographic projections (42.5%), table movement while acquisition (25.7%) and resolution incompatibility (15%). From 115 patients with analyzable pre-PCI vFFR, 74 (64.3%) showed agreement with the respective FFR results in terms of positive (≤0.80) vs negative (>0.80) FFR. Pearson's correlation coefficient between them was 0.449 (p < 0.0001). From 104 lesions with analyzable post-PCI vFFR, 94 had availability of FFR, 74 (78.7%) of which showed agreement between the vFFR and FFR. Pearson's correlation between the values was 0.115 (p = 0.2703)., Conclusion: vFFR could be analyzed in about one-third of previously completed angiographies and a weak correlation was seen between vFFR and FFR. Our results show the importance of following the pre-specified requirements for vFFR analysis. Further studies are needed to validate the software in different settings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Absorb bioresorbable vascular scaffold (BVS) promised to avoid some of the disadvantages of its metal predecessors. Even though it has been taken off the market, limited data is available about its use in coronary chronic total occlusion (CTO) and its performance in overlap segments, which would be of special research interest due to its large thickness. This data is still pertinent since the platform of bioresorbable devices has not been abandoned, with several companies working on it. We aimed to compare healing and performance between overlap (OL) and non-overlap regions (NOL) of CTO lesions treated with BVS, using optical coherence tomography (OCT). Fourteen patients with overlapping BVS were included from the GHOST-CTO registry, resulting in 25 OL and 38 NOL regions. OCT based parameters were compared between OL and NOL groups at baseline (post-implantation) and 12-month follow-up. The mean age was 61.7 ± 7.2 years and 12 (86%) were males. Twelve (86%) patients underwent PCI for stable coronary artery disease and 2 (14%) had unstable angina. At 12-month follow-up, mean lumen area decreased in both NOL and OL regions, but the decrease was significantly larger in the OL region (NOL - 0.7 ± 1.33 vs. OL - 2.4 ± 1.54 mm 2 ; p = 0.002). Mean scaffold area increased in both regions, but increased significantly more in NOL ( + 1.1 ± 1.54 vs. + 0.4 ± 1.16 mm 2 ; p = 0.016). The percent of uncovered struts was lower in the OL group (5.0 ± 6.6% vs. 3.75 ± 8.7%, p = 0.043), whereas the percentage of malapposed struts was similar (0.3 ± 0.5% vs. 0.7 ± 2.3%, p = 0.441). Neointimal hyperplasia (NIH) was more pronounced in the OL region (0.13 ± 0.04 vs. 0.24 ± 0.10 mm 2 , p = 0.001). The OL and NOL segments showed comparable healing in terms of coverage and malapposition. However, NIH was more prominent in OL region. The long-term clinical implications of these findings needs further evaluation. The present study provides important insights for future development of BVS technology.

Background: Treatment of psoriatic nail disease is challenging, and dystrophic psoriatic nails can get secondarily infected with fungi., Methods: This 2-year, matched case-control study was conducted at three tertiary care centers of Karachi, Pakistan. Data were collected from patients with nail psoriasis as cases with age- and gender-matched controls. A detailed questionnaire was filled for all study participants. Nail Psoriasis Severity Index (NAPSI) scoring tool was used to assess dystrophy. Fungal infection was inferred by nail clippings for fungal hyphae and culture., Results: Among 477 participants, 159 cases and 318 controls completed the study. Their mean age was 44 years, and one-third were female. Fungal culture positivity was statistically significant in cases as compared to the control group (P < 0.001). The most frequent species identified was Candida parapsilosis in both cases and controls. Body mass index, NAPSI scoring, socioeconomic status, elevated diastolic blood pressure, smoking status psoriasis among first-degree relatives, and longstanding disease of more than 10 years were significant factors in univariable analysis. Multivariable logistic regression identified independent factors like low to middle socioeconomic status, history of psoriasis in first-degree relative, current smoker, and obesity., Conclusion: We found nearly one-third of the psoriatic patients with nail involvement having concomitant fungal infection. We emphasize that nail clipping for fungal smear and culture should be advised to those patients with coexisting factors found significant in our study results. This opinion can be incorporated in psoriasis management guidelines for improving treatment of psoriatic nails., (© 2019 The International Society of Dermatology.)

Background: The vector-borne cutaneous leishmaniasis (CL) is endemic in several regions of Pakistan mainly affecting poor populations. Host genetic factors, particularly SLC11A1 (solute carrier transmembrane protein) within macrophages, play a crucial role in disease pathology and susceptibility. Association of SLC11A1 with cutaneous leishmaniasis, a neglected tropical disease, is not well established. Inconsistencies have been observed within different populations worldwide with respect to genetic susceptibility. This study was designed to investigate genetic variation(s) in SLC11A1 and to assess possible association with cutaneous leishmaniasis in Pakistan., Results: Eight polymorphisms (rs2276631, rs3731864, rs2290708, rs2695342, rs201565523, rs17215556, rs17235409, rs17235416) were genotyped across SLC11A1 in 274 patients and 119 healthy controls. Six polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing. Two single nucleotide polymorphisms were analyzed with newly designed semi-nested PCR assays. Case-control analysis showed no association between selected polymorphisms in SLC11A1 and cutaneous leishmaniasis. No significant difference was observed in the distribution of alleles between leishmaniasis patients and healthy individuals. Strong pairwise linkage disequilibrium was observed between rs2276631 and rs2290708 (r 2  = 64); and rs17235409 and rs17235416 (r 2  = 78)., Conclusions: This study shows that genetic variations in the candidate gene SLC11A1 do not affect susceptibility to cutaneous leishmaniasis in the sample population from Pakistan.

Background: Human immunodeficiency virus (HIV)/leishmaniasis coinfection is a matter of deep concern worldwide. CC chemokine receptor 5 (CCR5) functions as a co-receptor for HIV entry into host immune cells with an elevated expression observed during leishmaniasis, promoting parasite persistence. A 32 bp deletion (Δ32) in the CCR5 gene provides protection against HIV infection and increased resistance to Leishmania infection., Methods: In this study, CCR5-Δ32 distribution within Pakistani population with cutaneous leishmaniasis was investigated to evaluate genetic susceptibility to HIV infection. CCR5-Δ32 polymorphism was analyzed in 276 leishmaniasis patients and 119 uninfected healthy controls. Genotypic and allelic frequencies were evaluated and tested for Hardy-Weinberg equilibrium (HWE)., Results: The overall Δ32 allele frequency was 6.58% of the population (n = 395). There was a significant difference (p < 0.05) in the geographical distribution of Δ32 allele which was higher in the northern region of the country when compared with the south. Five individuals were identified to be homozygous for the Δ32 allele which has not been reported before from Pakistan. However, no significant association was observed between CCR5-Δ32 and cutaneous leishmaniasis., Conclusion: The higher frequency of CCR5 wild-type allele among leishmaniasis patients may suggest an increased risk of HIV infection and also support its facilitative role in Leishmania infection., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of this study was to detect an 811 bp filaggrin (FLG) gene fragment known to carry a mutation 2282del4 which causes ichthyosis vulgaris. Seven clinically examined ichthyosis vulgaris families were included in this study. An 811 bp FLG gene fragment was targeted in the genomic DNA of all the members of the seven families by PCR amplification using known primers RPT1P7 and RPT2P1. Successful amplification of an 811 bp FLG gene fragment in all the families suggested the possible role of the 2282del4 mutation in causing ichthyosis vulgaris in Pakistani population.

Objective: To compare the clinical outcomes of a loading dose regimen of quinine with a uniform dose regimen in patients with severe falciparum malaria., Methods: A retrospective chart review of 315 patients admitted with severe falciparum malaria and treated with quinine at a tertiary care teaching hospital of Karachi, Pakistan during 1999-2006 was conducted. Group A with 103 patients (32.7%) was given an initial loading dose of quinine while group B with 212 patients (67.3%) did not receive the loading dose. The two groups were compared in terms of reduction of parasite load, resolution of fever, recovery of consciousness and incidence of adverse effects. Outcome parameters were measured on the third day of therapy., Results: More individuals in group A (62.1%) were afebrile as compared to group B (54.7%) at day 3 of therapy. Patients in group B showed greater reduction in parasitaemia (47.2% at baseline to 4.7% on day 3) as compared to group A (56.3 % at baseline to 9.7% on day 3). Following therapy, fewer patients in group B had altered consciousness (7.1% at baseline to 4.7% on day 3) as compared to patients in group A (7.8% at baseline to 5.8% on day 3). However, these associations were not statistically significant. The incidence of thrombocytopenia was higher in Group A (5.8%) as compared to Group B (0.9%)., Conclusion: Although quinine loading dose may be more effective than uniform dose in rapid fever clearance; it also appears to be associated with higher toxicity. Uniform dose of quinine may be prescribed in severe falciparum malaria in view of its better safety profile.

Background: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan., Main Observations: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced. Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids)., Conclusion: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.

Objective: To target and amplify a 1.5 kb FLG gene fragment known to carry R501X mutation responsible for causing ichthyosis vulgaris., Study Design: A case series., Place and Duration of Study: Centre for Molecular Genetics, University of Karachi and Dermatology Department, Jinnah Postgraduate Medical Centre (JPMC), Karachi, from October 2007 to December 2008., Methodology: Clinically examined seven ichthyosis vulgaris families were included in this study. The 1.5 kb FLG gene fragment was located in the genomic DNA of both the affected (patients) and unaffected (normal, controls) members of the families by PCR amplification using known primers FilF3 and RPTIP6., Results: Amplification of 1.5 kb FLG gene fragment was successful in four families while one family showed amplification of the gene fragment in 3 members (one affected and two normal). Two families showed no amplification., Conclusion: The results obtained during this study suggested the possibility of the R501X mutation as being one of the major causes of ichthyosis vulgaris in Pakistan. In addition, the study also revealed the possibility of the presence of novel FLG gene mutations in our population.

Objective: To study the characteristics of patients admitted with drug overdose caused either by accidental overdose of the prescribed medications or as an act of deliberate self harm (DSH) at a tertiary care hospital in Karachi, Pakistan., Methods: A retrospective case series review was conducted at the Aga Khan University Hospital from January 2002 to October 2006. Three hundred and twenty four adult patients admitted with drug overdose were included in the study., Results: Our sample group revealed mean age of 36.2 +/- 17.0 years, more females (59%), housewives (34%), and students (20%). Fifty six percent of patients committing DSH were married (p = 0.001), 81% needed in-patient psychiatric services (p = 0.016) of whom a significantly high number (38%) refused it. Domestic and social issues were rated highest among DSH group (p = 0.003), depression among females was common (p = 0.028) and Benzodiazepines (41%) was the most frequently used drug (p = 0.021). Sub-group analysis of accidental overdoses revealed mean age of 45.6 +/- 19.6 years, single (75.4%) and males (54.1%). Drugs used were mainly Benzodiazepines (18%) followed by Opioids (11%), Antiepileptics (10%) and Warfarin (10%)., Conclusion: Our study showed that depressed housewives are at greater risk for DSH. Domestic and social issues were rated highest and Benzodiazepines were the most commonly used agents. Most of our patients refused inpatient psychiatric treatment leading us to believe that general awareness of psychiatric illnesses is imperative in our community. High number of accidental overdoses is alarming in older, single males convincing us to believe that existing pharmacy system needs further evaluation and modification.

Objective: To survey Internal Medicine trainees' future career choices and factors influencing their decision-making., Design: Cross-sectional study., Place and Duration of Study: The Aga Khan University Hospital, Karachi, from November 2006 to January 2007., Subjects and Methods: A standard questionnaire was administered to the residents and Interns working in the Department of Internal Medicine of The Aga Khan University Hospital. The questionnaire covered demographic details, specialty choice, work-time distribution and factors influencing career choice. Descriptive statistics were applied., Results: A total of 49 doctors participated with 57% females; and 43% males, having 33% interns and 67% residents. A minority (22%) opted for internal medicine, while 78% selected sub-specialties with cardiology (20%) being the most sought- after sub-specialty. Majority (69%) wanted to spend more time in clinical activities compared to administration (18%) or research (13%). Majority (92%) wanted to work in an academic setting. Availability of a structured training program (61%), ability to practice broad area of medicine (41%) and prestige of the specialty (41%) highly influenced their career choices. Forty one (82%) wanted to proceed abroad for further training and 80% wanted to eventually practice in Pakistan., Conclusion: Most of the interviewed under-training physicians wanted to pursue sub-specialty. Clinical work was more attractive compared to research. A structured training program was detrimental in affecting their choices. Majority wanted further training abroad but eventual settlement in Pakistan. The study results can help us create the basis for reforming the current training programs.

Introduction: Our aim was to determine the characteristics of patients presenting with syncope at a tertiary care hospital in Karachi, Pakistan., Methods: A review of medical records was conducted retrospectively at the Department of Medicine, Aga Khan University Hospital, Karachi. Patients aged 16 and above, admitted from January 2000 to December 2005 with the diagnosis of syncope made by the attending physician were included., Results: A total of 269 patients were included (75% males, mean age: 57.4 years). Neurogenic (vasovagal) syncope was the most common cause (47%), followed by cardiogenic syncope (18%) and orthostatic syncope (9%). A total of 24% were discharged undiagnosed. Twenty patients (7.4%) did not have any prodrome. Common prodromal symptoms included dizziness (61%), sweating (25%), palpitations (19%), nausea/vomiting (19%) and visual symptoms (17%). The distribution of symptoms according to cause of syncope revealed only breathlessness to be significantly associated with cardiogenic syncope (p = 0.002). Most patients with cardiogenic syncope were aged above 40 (98%, p < 0.001), had coronary artery disease (72%, p < 0.001) and abnormal electrocardiogram at presentation (92%, p < 0.001)., Conclusion: Despite differences in burden of diseases, our findings were similar to those of published syncope literature. Further studies are needed to develop a protocol to expedite the evaluation and limit the work-up and admission in low-risk patients.

Background: This study was carried out to determine growth of dermatophytes using human stratum corneum in vitro and the degrading effect of Keratinases (Proteinases) on stratum corneum for a complete understanding of the host parasite relationship., Method: Trichophyton rubrum isolates derived from patients with tinea cruris infections were obtained from the Department of Medical Microbiology, University Hospital of Wales, U.K. Human stratum corneum sterilized with ethylene oxide was used as a nitrogen source in agar culture medium plates., Result: Fungal growth took place in plates which contained human stratum corneum particles while there was no growth in the plates without stratum corneum at three weeks after initiation. There was a gradual disappearance of the particles of stratum corneum from the plates at the end of the third week, Conclusion: The growth of organisms in plates with human stratum corneum and their disappearance at third week suggested that stratum corneum was not only source of nutrition for the dermatophytes, but also the growing fungal mycelia and the proteinases induced by them were playing a part in the digestion of granules and thus may have an important role in the pathogenesis of dermatophyte infections.

Background: An association between HCV infection and lichen planus is uncertain because the prevalence of HCV infection in patients with lichen planus varies considerably from one geographic area to another. The purpose of this study was to determine the frequency of anti-HCV antibodies and its association with various clinical types of lichen planus in Mekkah, Saudi Arabia., Methods: A total of 114 cases of lichen planus were selected for the study. These were divided into four categories, including patients with skin lesions, skin and oral lesions, and oral or genital lesions alone. The sera of these patients were tested for HCV antibodies by means of a third-generation ELISA and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were simultaneously determined. A group of 65 volunteers served as a control group., Results: Of the 114 patients with lichen planus, 30 had HCV antibodies (26.3%). In the 65 control group subjects anti-HCV antibodies were observed in 3 volunteers (4.6%). There was a significant difference between the two groups (P<0.0001). The ALT was raised in 22 patients and the AST level was elevated in 14 of the 114 cases of lichen planus. In the control group, the AST level was raised in 3 of the 65 controls while 2 had an elevated ALT level. The number of patients with an abnormal transaminase level also significantly differed in the two groups., Conclusion: A high prevalence of HCV infection was detected in patients with lichen planus. These results support a possible relationship between lichen planus and hepatitis C.

Autosomal recessive ectodermal dysplasia with acanthosis nigricans is termed Lelis' syndrome. It is a rare condition and one case is described with overall clinical, dermatological and dental findings.

Background: The pilgrimage (Hajj) to the holy mosque in the city of Makkah takes place once every year and during this huge gathering skin diseases are quite common due to hot weather and over crowding. The aim of this study was to collect and report data regarding different dermatological problems occurring during the holy month of Zil-hajj., Methods: Data regarding skin diseases was collected from pilgrims which were examined and diagnosed clinically at the Department of Dermatology King Abdul Aziz Hospital, during the month of Zil-Hajja of the year 2000. These patients were referred from various primary health centers, medical hajj missions of various countries and Children and Maternity hospital in Makkah., Results: During the month of Zil-hajja of the year 2000, 1510 cases were seen, of these 1143 were males and 367 were females. The criteria for diagnosis for most of the cases were mainly clinical. The highest number of patients was in the age group of 20-50 years. Eczemas of different types were the most common skin disease observed in these pilgrims, intertrigo was the next most common presenting condition this was followed by fungal and bacterial infections., Conclusion: A high frequency of skin diseases such as eczemas, intertrigo, pyoderma and fungal infections was found among the pilgrims. More detailed studies regarding skin conditions during this season would enable us to have better understanding of skin problems there management and prevention in full.

To understand the significance of proteolytic enzymes in the pathogenesis of dermatophyte infections, we have studied the expression of proteolytic activity in vitro. Cultures were extracted after 1, 2, 3, 4 and 5 weeks of growth and the proteolytic activity measured by a peptide release assay using human stratum corneum as a substrate. Maximum activity was noted at 3 weeks which corresponded to the dissolution of the stratum corneum particles. Isolates of Trichophyton mentagrophytes and Trichophyton rubrum from 42 patients with tinea pedis or tinea unguium were established on 2% glucose peptone plates. Using the peptide release assay it was found that after 3 weeks culture, T. mentagrophytes showed higher activity that T. rubrum in tinea pedis (2044 +/- 1067 micrograms protein released h-1 mg-1, n = 13 compared to 828 +/- 614 micrograms protein released h-1 mg-1, n = 13). In tinea unguium, the values at 3 weeks were generally lower. Trichophyton mentagrophytes activity was 837 +/- 121 micrograms protein released h-1 mg-1 (n = 3) compared to 470 +/- 271 micrograms protein released h-1 mg-1 (n = 13) for T. rubrum. Thus, as well as a variation in activity between the two species, there appears to be a variation in site in terms of expression of activity.

In this study we have measured the mean hyphal length as a function of the density of infection in skin surface biopsies from patients suffering from infection with different species of dermatophyte. The tissue response in the epidermis and dermis of these patients was evaluated for the degree of eczematization (epidermal thickening, spongiosis and dermal infiltrate) in periodic acid Schiff stained histological sections, employing visual analogue scales. There was no correlation between mean hyphal density and the degree of eczematization.