Hybrid odontogenic lesions: A case series of a rare entity.

Background: The occurrence of hybrid odontogenic lesions with two or more morphologically distinct components is a rare phenomenon and poses a diagnostic challenge. We aimed to study the clinical, radiological, and pathological features and behavior of hybrid odontogenic lesions, to enhance awareness about these rare lesions. Method: Hematoxylin and Eosin slides of hybrid odontogenic lesions diagnosed between January 01, 2012 and December 31, 2020, were reviewed. Demographic and radiological information were obtained from the patient's medical records. Results: 8 cases were diagnosed with a mean age of 19.1 years and male to female ratio of 1:1.7. Involvement of mandible was more common (n = 5) as compared to maxilla (n = 3). All patients presented with swelling for an average of 9.75 months (3-25 months) duration. Bleeding, loose teeth, pain and facial asymmetry were reported in 5,3, 3, and 2 cases, respectively. Radiologically, 7 cases were well demarcated, 75% cases (n = 6) were radiolucent, and average radiological size was 4.8 cm. All patients were managed with surgery alone. 5 cases (62.5%) underwent enucleation and curettage, while local excision, en-block resection and segmental mandibulectomy were performed in 1 case each. Histologically, ossifying fibroma/cemento-ossifyiong fibroma were the most lesion, occurring in 5 cases (62%), followed by giant cell granuloma like lesions (GCG) i.e., central and peripheral giant cell granuloma (n = 3), Adenomatoid Odontogenic tumor (AOT) (n = 2), and DC (n = 2), ameloblastic fibroma (AF) (n = 1), Ameloblastoma (n = 1), calcifying odontogenic cyst (COC) (n = 1), and complex odontoma (n = 1). No evidence of recurrence was noted after 4-99 months of surgery (mean: 32.9) in cases with available data (n = 7). Long-term complaints included facial asymmetry (n = 2) and pain (n = 1). Conclusion: Most hybrid odontogenic lesions affect young females in the second decade of life and commonly show COF and OF as hybrid components. A conservative approach to management appears adequate.

Ensuring competence of essential skills: clinical examination for final year medical students.

OBJECTIVE: To ensure competence of essential skills of final year medical students in clinical examination by identifying essential skills and by revisiting and practising them before the examination. Methods: The cross-sectional study was conducted at the Aga Khan University, Karachi, from February to November, 2019, and comprised final year medical students and internal examiners from various academic disciplines. An overview of the organisational context, exam structure and process was noted. RESULTS: There were 96 medical students. The four key areas highlighted were development of the list of essential skills across five years of undergraduate medical curriculum with consensus from all disciplines, student motivation for attendance in practice sessions, unfamiliarity of examiners with the assessment tool, and the need for capacity-building. The key areas were based on the feedback received from all the stakeholders, and post-hoc analysis. Conclusion: This form of assessment would enable a thorough analysis of the preparedness of the students to function as independent physicians as undifferentiated doctor at the start of their careers as interns, and improve the quality of subsequent exams based on feedback and suggestions of faculty and students.

Recruitment, consent and retention of participants in randomised controlled trials: a review of trials published in the National Institute for Health Research (NIHR) Journals Library (1997-2020).

OBJECTIVES: To review the consent, recruitment and retention rates for randomised controlled trials (RCTs) funded by the UK's National Institute for Health Research (NIHR) and published in the online NIHR Journals Library between January 1997 and December 2020. DESIGN: Comprehensive review. SETTING: RCTs funded by the NIHR and published in the NIHR Journals Library. DATA EXTRACTION: Information relating to the trial characteristics, sample size, recruitment and retention. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the recruitment rate (number of participants recruited per centre per month). Secondary outcomes were the target sample size and whether it was achieved; consent rates (percentage of eligible participants who consented and were randomised) and retention rates (percentage of randomised participants retained and assessed with valid primary outcome data). RESULTS: This review identified 388 individual RCTs from 379 reports in the NIHR Journals Library. The final recruitment target sample size was achieved in 63% (245/388) of the RCTs. The original recruitment target was revised in 30% (118/388) of trials (downwards in 67% (79/118)). The median recruitment rate (participants per centre per month) was found to be 0.95 (IQR: 0.42-2.60); the median consent rate was 72% (IQR: 50%-88%) and the median retention rate was estimated at 88% (IQR: 80%-97%). CONCLUSIONS: There is considerable variation in the consent, recruitment and retention rates in publicly funded RCTs. Although the majority of (6 out of 10) trials in this review achieved their final target sample; 3 out of 10 trials revised their original target sample size (downwards in 7 out of 10 trials). Investigators should bear this in mind at the planning stage of their study and not be overly optimistic about their recruitment projections.

Tracheobronchopathia osteochondroplastica: a cause of chronic cough and haemoptysis.

Tracheobronchopathia osteochondroplastica (TPO) is a rare disorder of the tracheopulmonary tree characterised by osseous and cartilaginous submucosal nodules projecting into the tracheal lumen, sparing the posterior tracheal membranous wall. Symptoms are non-specific and may include dry cough, hoarseness, dyspnoea, recurrent pneumonia and occasionally haemoptysis. A fibreoptic bronchoscopy showing multiple tracheal nodules followed by pathological biopsy is required to reach the final diagnosis. Here, we report two cases of TPO, both with history of biomass fuel exposure and almost similar clinical presentions with chronic cough, shortness of breath and intermittent haemoptysis. They both underwent fibreoptic bronchoscopy showing multiple tracheal nodules whose histopathological analysis showed the diagnosis of TPO. Both patients were treated conservatively and remained in good health afterwards. Physicians should be aware about the need of advanced surgical procedures including endotracheal stent placement in more severe cases.

Impact of humanities and social sciences curriculum in an undergraduate medical education programme.

OBJECTIVE: To evaluate the impact of humanities and social sciences curriculum in an undergraduate medical education programme. METHODS: The qualitative study was conducted from May 2016 to May 2017 at a private medical college in Karachi where humanities and social sciences subject is an art of the undergraduate curriculum as a 6-week module at the start of Year 1 of the five-year programme. Focus group discussions were held with students from all the five years as well as with faculty related to humanities and social sciences, basic sciences and their clinical counterparts. The views of alumni of the undergraduate programme who are now members of the faculty at the institution were also explored and semi-structured interviews were conducted with institutional academic leaders. MAXQDA software was used to identify the themes for analysis. RESULTS: Of the 50 participants, 27(54%) were students, 21(42%) were faculty members and 2(4%) were academic leaders. From the 11 sub-themes, 5 themes were identified: Expectations, Strengths, Challenges, Way forward, and Institutional role and responsibility. Faculty members perceived humanities and social sciences as encouraging creative and critical thinking, boosting students' confidence and positively impacting their behaviour. Student perception seemed to change as they progressed through the years and they appreciated its impact at different stages. CONCLUSIONS: The existing humanities and social sciences curriculum can be further strengthened by integrating contents throughout the five-year programme and continuing it as a longitudinal theme rather than limiting it to a one-time exposure at the start of the programme.

Idiopathic pulmonary hemosiderosis - A rare cause of chronic anemia.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease marked by alveolar bleeding and accumulation of hemosiderin in the lungs. Here we present three cases of IPH. The first case is of a 26-year-old male with anemia, hemoptysis and dyspnea. Bronchoscopy confirmed diffuse alveolar hemorrhage (DAH). A diagnosis of IPH was made after ruling out other causes of DAH and observing good response to steroids. The patient's condition improved with prednisolone and azathioprine. The second case is of 26-year-old female with severe anemia. Imaging suggested IPH and lung biopsy confirmed it. She died shortly afterwards. The third case is of a 7-year-old male with chronic anemia. CT was suggestive of IPH and lung biopsy confirmed the diagnosis. Later, patient developed posterior reversible encephalopathy syndrome (PRES). This patient is stable on azathioprine and prednisolone. We aim to emphasize the importance of considering IPH as a differential in patients with DAH or chronic anemia.

CDH1 gene mutation in early-onset, colorectal signet-ring cell carcinoma.

AIM: Colorectal signet-ring cell carcinomas (SRCC) are highly malignant tumours with poor prognosis that disproportionately affect younger patients. There is growing evidence of a unique set of molecular features that separate SRCC from conventional colorectal adenocarcinoma. Identification of these distinct features may have diagnostic and prognostic significance for patients and families. CDH1, which encodes E-cadherin, a cell adhesion protein, is commonly mutated in gastric SRCC and our study aimed to identify whether CDH1 mutation was also a common phenomenon in colorectal SRCC. METHODS: DNA was extracted from formalin-fixed paraffin embedded tumour tissue, the CDH1 gene was analysed by next generation sequencing and the pathogenicity of mutations assessed in silico. Sections cut from the same blocks were immunostained to identify the presence of the E-cadherin protein. RESULTS: We found 8 CDH1 mutations that meet our inclusion criteria in seven of 11 samples. Of these, five (from four patients), were likely to be germline mutations. E-cadherin staining was absent or markedly reduced in all of the seven samples with CDH1 mutation. CONCLUSION: Our finding of CDH1 mutations in a proportion of signet-ring cell carcinomas and associated reduction in E-cadherin in these tumours supports previous findings of a role for mutation of this gene in the development of this disease. In addition, the finding of likely germline mutations suggests that a subset of these tumours may be familial. Loss of E-cadherin staining in the absence of CDH1 mutations however also suggests a role for environmental factors in a subset of these tumours.

Mutational landscape of head and neck squamous cell carcinomas in a South Asian population.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is among the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA analysis (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel recurrent mutations in ASNS (asparagine synthetase) that may affect substrate binding, and variants in driver genes including TP53, PIK3CA, FGFR2, ARID2, MLL3, MYC and ALK. Using the IntOGen platform, we identified MAP kinase, cell cycle, actin cytoskeleton regulation, PI3K-Akt signaling and other pathways in cancer as affected in the samples. This data is the first of its kind from the Pakistani population. The results of this study can guide a better mechanistic understanding of HNSCC in the population, ultimately contributing new, rational therapeutic targets for the treatment of the disease.

Primary pulmonary plasmacytoma presenting with rare IgG lambda monoclonal gammopathy.

Extramedullaryplasmacytoma (EMP) represents a peculiar and typically progressive malignancy that can originate outside the bone marrow. Primary pulmonary plasmacytoma (PPP) is a rare subset of EMP, confined to the lung. A 55-year-old man, diabetic, non-smoker presented to our clinic with a right chest wall swelling. A routine chest radiograph showed a well-circumscribed opacity in the right upper lung zone. A CT of the chest revealed a large right upper lobe mass with extensive local infiltration. Biopsy and immunohistochemical evaluation led to a diagnosis of PPP. Screening for multiple myeloma was negative. Serum immunofixation showed an IgG lambda monoclonal gammopathy, found in a minority of PPP patients. In view of disease extent, treatment with chemotherapy and radiotherapy was initiated. The patient is currently in out patient follow-up and has shown a favourable response to the treatment with a considerable decrease in serum IgG levels.

Correlation of Trainees' Selection Scores with their Subsequent Performance during Specialty Training in Anesthesiology.

OBJECTIVE: To determine the correlation of trainee selection scores (TSS) with subsequent performance in anesthesiology trainees at a university hospital. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from August 2016 to January 2017. METHODOLOGY: Data were collected on 44 anesthesiology trainees completing their training between 2009 and 2015. TSS consisted of entrance test, final-year medical school scores, and interviews. Assessment included written tests, viva voce, and clinical assessment. Non-parametric Spearman rank correlation coefficient was computed to assess the relationship between scores. RESULTS: Weak correlation was found between TSS and overall assessment scores for first three years of training. Correlation of TSS with clinical component of assessment was weak throughout training, while it was moderately significant with cognitive component of assessment in third and fourth years of training. Correlation between interview scores and cognitive as well as clinical assessment was non-significant. TSS showed weak correlation with success in exit level examination. CONCLUSION: Correlation between overall TSS and assessment scores was weak for first three years of training, and becoming moderately positive in later years of training. Cognitive component of TSS had moderately positive correlation with cognitive assessment, but not with clinical performance. Anesthesiology training programmes need to strengthen their selection criteria; and development of structured interviews might prove useful. Future research should focus upon identifying most useful traits in selecting high performers in anesthesiology training.

An unusual presentation of diffuse large B-cell lymphoma with ureteric involvement: A case report.

INTRODUCTION: Non-Hodgkin's lymphomas are a heterogeneous group of malignancies in the lymphoid system and ureteric involvement by non-Hodgkin's lymphoma is very rare. CASE PRESENTATION: We present a 37-year-old male, presenting with lower urinary tract symptoms and right flank pain. Initially, he presented with lower urinary tract symptoms without having any evidence of urinary tract infection and was managed for nonspecific cystitis. His ureteral histopathology report indicated a diffused infiltration by malignant lymphoid cells and the final diagnosis revealed diffuse large B-cell lymphoma. His positron-emission tomography scan indicated stage 4 disease with skeletal involvement and he was then treated by rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and methylprednisolone chemotherapy. Later, he was also diagnosed with central nervous system lymphoma and died during his stay in the hospital. CONCLUSION: Primary diffuse large B-cell lymphoma of the ureter is extremely rare; however, it should be considered in the differential diagnosis for patients presenting with obstructive uropathy as its early detection is crucial for diagnostic and therapeutic treatment.

Value of Dedicated Research Time for IMGs in Obtaining Surgical Residency Training Positions: A 10-Year Review of Applicants from a Medical College in Pakistan.

OBJECTIVE: International Medical Graduates (IMGs) secured greater than 10% of all general surgery (GS) residency positions in the US during the past decade. The Match process remains competitive, with a significant number of IMGs performing dedicated research before residency application. The impact of such research remains largely unknown. We aimed to provide an objective analysis of the impact of dedicated research time on obtaining a categorical GS residency position. DESIGN: Data for National Resident Matching Program Match results from 2008-2017 was compiled from annual Match lists of the Aga Khan University, Medical College (Karachi, Pakistan). Medical graduates provided this information voluntarily each year. Data was exported to Microsoft Excel and used for descriptive and statistical analysis using SPSS. Candidates were divided into quasi-experimental groups based on their preference for direct application (no-research group, n = 64) or research prior to Match (research group, n = 20). RESULTS: A total of 84 IMG applicants matched into GS residency positions in the US within the past decade. Amongst these, 18 matched directly into categorical positions while 66 applicants secured preliminary spots. A total of 37 (56%) preliminary candidates eventually secured categorical GS residency positions. Research group applicants had an overall 85% (n = 17) success rate of obtaining a categorical position, while no-research group had a 59% (n = 39) success rate (chi-square test, p = 0.04). Success rate was 69% (n = 38) for male applicants and 57% (n = 17) for female applicants. Median time to a categorical position was 4 years (2-6) for the research group and 3 years (1-6) for the no-research group. CONCLUSIONS: Our quasi-experimental study demonstrated a higher success rate for Aga Khan University, Medical College applicants with significant research background in the US, compared to those who did not. Better social integration, enhanced mentorship available during research, overcoming of cultural and linguistic barriers and a perception as better qualified candidate can be some factors contributing to higher success rates.

Case Of Xanthogranulomatous Oophoritis.

Xanthogranulomatous inflammation is characterized by destruction of the tissues of the organ involved and replacement by chronic inflammatory cells such as lymphocytes, plasma cells, occasional neutrophils with or without multinucleated or Touton giant cells. Exact aetiology is not known but the theory of infection with organisms like Proteus, E coli, and Bacteroides fragilis is most popular. Xanthogranulomatous inflammation of the female genital tract is not common and usually involves the endometrium; however, xanthogranulomatous inflammation of the ovaries is a rare entity.

Hybrid peripheral nerve sheath tumors: report of five cases and detailed review of literature.

BACKGROUND: Hybrid peripheral nerve sheath tumors (PNSTs) have been recognized recently and were first included in the 4th edition of World Health Organization (WHO) Classification of Tumors of Soft tissue and Bone, published in 2013. These tumors show combined features of more than one type of conventional benign peripheral nerve sheath tumors. The most common combinations are those of schwannoma/perineurioma followed by combinations of neurofibroma/schwannoma and neurofibroma/perineurioma. A detailed literature review of published cases is presented. We have discussed the types and etiology, epidemiology and sites of localization, gross and microscopic appearances and immunohistochemical features of hybrid PNSTs and association of these tumors with tumor syndromes. CASE PRESENTATION: We have included five cases which were diagnosed in our department as we believe that publication of these new cases is relevant for the improved understanding of these specific tumors. Four of our five patients were males, mean age was 24 years. There was wide variation in the location of these tumors. Mean size of excised tumors was 5.5 cms in the greatest dimensions. Three out of five cases represented hybrid schwannoma/perineurioma histologically. No significant nuclear atypia, mitotic activity or necrosis seen. All five cases were completely excised. All five patients are alive and well at the time of writing with no recurrence. CONCLUSION: Hybrid PNSTs are distinct tumors and are usually benign. However, rare case reports have described local recurrence and at least two recent case reports have described malignant transformation in these tumors. Further studies on large number of cases are required to determine the exact pathogenetic basis of these tumors.

Stretching the boundaries of medical education A case of medical college embracing humanities and social sciences in medical education.

OBJECTIVE: Aga Khan University, a private medical college, had a vision of producing physicians who are not only scientifically competent, but also socially sensitive, the latter by exposure of medical students to a broad-based curriculum. The objective of this study was to identify the genesis of broad-based education and its integration into the undergraduate medical education program as the Humanities and Social Sciences (HASS) course. METHODS: A qualitative methodology was used for this study. Sources of data included document review and in-depth key informant interviews. Nvivo software was utilized to extract themes. RESULTS: The study revealed the process of operationalization of the institutional vision to produce competent and culturally sensitive physicians. The delay in the establishment of the Faculty of Arts and Sciences, which was expected to take a lead role in the delivery of a broad-based education, led to the development of an innovative HASS course in the medical curriculum. The study also identified availability of faculty and resistance from students as challenges faced in the implementation and evolution of HASS. CONCLUSIONS: The description of the journey and viability of integration of HASS into the medical curriculum offers a model to medical colleges seeking ways to produce socially sensitive physicians.

Has the inclusion of a longitudinally integrated communication skills program improved consultation skills in medical students? A pilot study.

BACKGROUND: Evidence highlights a lack of communication skills in doctors leading to dysfunctional consultations. To address this deficit, a private medical college instituted curricular reforms with inclusion of a longitudinal communication skills program. A pilot study was undertaken to evaluate the effectiveness of this program by comparing the consultation skills of medical students of this college with a medical college without a communication skills program. METHODS: A 4-station Objective Structured Clinical Examination (OSCE) was conducted in the third and final year. Mann-Whitney U-test was used to compare the difference in the distribution between OSCE stations total and construct scores. RESULTS: At the end of the third year, 21 (31.34%), students of the study site (medical college 1 [college with integrated longitudinal communication skills program]) and 31 (46.26%) students from the comparison site (medical college 2 [comparable college without communication skills program]) consented. Medical college 1 achieved a significantly higher overall mean total station score of 68.0% (standard deviation [SD] =13.5) versus 57.2% (SD = 15.4) (P < 0.001). Significantly higher mean scores were achieved on three stations. At the end of the final year, 19 students (29.3%) from medical college 1 and 22 (34%) students from medical college 2 consented. The difference in overall mean total station score reduced from 9.2% to 7.1% (70.2) (SD = 13.7) versus 63.1 (SD = 15.2) (P = 0.004). The mean scores of both colleges decreased in "Patient presenting with Hepatitis C Report" station (P values 0.004 and 0.775) and in "Patient Request for Faith Healing Therapy in Diabetes Mellitus" station (P values 0.0046 and 0.036), respectively. CONCLUSION: Longitudinal communication skills in an undergraduate curriculum positively impacted consultation skills. Community-based training and faculty development are required to develop effective patient-centered consultation skills.

Sporadic Early Onset Colorectal Cancer in Pakistan: a Case- Control Analysis of Microsatellite Instability.

BACKGROUND: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged ≤45 years) with controls (>45 years). MATERIALS AND METHODS: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features. RESULTS: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls. CONCLUSIONS: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms.

Commonest Cancers in Pakistan - Findings and Histopathological Perspective from a Premier Surgical Pathology Center in Pakistan.

CONTEXT: There are no recent authoritative data about incidence and prevalence of various types of cancers in Pakistan. AIM: To determine the frequency of malignant tumors seen in our practice and provide a foundation for building a comprehensive cancer care strategy. MATERIALS AND METHODS: 10,000 successive cases of solid malignant tumors reported in 2014 were included. All cases had formalin fixed, paraffin embedded specimens available and diagnosis was based on histological examination of H and E stained slides plus ancillary studies at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. The latest WHO classifications were used along with the latest CAP protocols for reporting and the most updated TNM staging. RESULTS: There were 9,492 (94.9%) primary tumors while 508 (5.1%) were metastatic. Some 5,153 (51.5%) were diagnosed in females and 4,847 (48.5%) in males. The commonest malignant tumors in females were breast (32%), esophagus (7%), lymphomas (6.8%), oral cavity (6.7%) and ovary (4.8%), while in males they were oral cavity (13.9%), lymphomas (12.8%), colorectum (7.9%), stomach (6.9%) and esophagus (6.6%). Malignant tumors were most common in the 5th, 6th and 7th decades. About 8% were seen under 20 years of age. CONCLUSIONS: Oral cavity and gastrointestinal cancers continue to be extremely common in both genders. Breast and esophageal cancers are prevalent in females. Lung and prostate cancer are less common than in the west. Ovarian cancer was very common but cervix cancer was less so.

Quality improvement initiatives by Aga Khan Health Service in the mountains of northern Pakistan.

Improving health care quality in a resource constraint environment in an emerging economy that is in a hard-to-reach geographic terrain can become a challenge especially when it has to follow the international standard which AKHS, P envisions to implement across the nation in all of its health facilities. Healthcare of the nation is a responsibility which is shouldered by both the government and the private sector. Private-sector, however, remains under pressure as its resource size is limited and it remains subject to stringent regulation and quality control requirements regardless of whether it is in the remotest corner of the country where proper land routes are either lacking or not safe. This article shares the unique experience of AKHS, P in achieving ISO 9001:2008 International Quality Management System Certification. Particularly at one of the "world's highest valleys -situated at Gilgit Baltistan at an altitude of 13,083 ft. above sea level in Northern Pakistan. The experience was unique in terms of demonstrating and recording how a quality management system can be implemented in one of the most difficult to reach areas where compliance to international quality standards was previously unthinkable.