Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

BACKGROUND: Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS: In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS: We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION: Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

Assessing the knowledge, attitude and practice of osteoporosis among Pakistani women: A national social-media based survey.

BACKGROUND: There are numerous risk factors for osteoporosis and understanding and recognizing these risk factors is critical when deciding whether to take preventive measures. It is critical to reduce the healthcare expenditure burden of the Pakistani population by raising awareness and implementing osteoporosis-preventable measures. This survey aims to assess the knowledge, attitudes, and practices (KAP) of Pakistani women as well as their misconceptions about osteoporosis. METHODS: A cross-sectional survey was conducted from August 2021 to January 2022 by the Bone & Mineral Disease research group at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, with exemption from the ethical review committee. Using snowball sampling, a validated Osteoporosis Prevention and Awareness Tool (OPAAT) was disseminated online via social media. With informed consent, 400 Pakistani women aged ≥ 18 years were included in the study. SPSS Statistics version 25.0 was used for data analysis. Chi-square test for association and Fisher-exact test were applied, and significance level was α<0.05. RESULTS: Based on the OPAAT scores of all (n = 400) participants, 22% (n = 88) had low knowledge, 44% (n = 176) had average knowledge, while 34% (n = 136) had good knowledge of osteoporosis. The most common misconceptions were about age-related risk, presentation of symptoms, radiation risk, associated risk factors like tooth loss, osteoarthritis, and knowledge about predictors of bone health. CONCLUSION: Adult Pakistani women have a fair understanding of osteoporosis, but the OPAAT tool clarifies some common misconceptions. There is a need to develop educational strategies to increase the knowledge of osteoporosis among Pakistani adults and to promote a bone-healthy lifestyle.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context.

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis. PURPOSE: Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan. METHODS: The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). RESULTS: The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. CONCLUSION: The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000-4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis.Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan.The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)-clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update from American Association of Clinical Endocrinology (AACE). The SG was "adoloped" to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000-4000 IU of vitamin D in patients with obesity, malabsorption, and old age. The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000-4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

Need for Development and Validation of Sarcopenia Screening Tools in Pakistan.

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Practices of vitamin D supplementation leading to vitamin D toxicity: Experience from a Low-Middle Income Country.

INTRODUCTION: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects. METHODOLOGY: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. The statistical analysis was performed using the Microsoft Excel 2016. RESULTS: Over a year period 105398 subjects were tested for serum 25OHD, of which 0.34% (n = 364) subjects had 25OHD level of >150 ng/ml. After satisfying exclusion criteria 186 subjects (78 were <18 years of age and 108 were adults) were included in final analysis. All of these were using VD supplements and the main indications were delayed growth/short height (43.7%, n = 34) and aches or pains in (54.6%, n = 59) in pediatric and adult subjects respectively.Most of the subjects were taking supplements orally (74.1%, n = 138). Commonly prescribed preparation in adults and pediatric was 200,000 IU (70.4%, n = 76) and 400 IU (35.9%, n = 28) respectively. Most subjects took supplements for 1-3 months (68.3%, n = 127). Stated total supplementation ranged from 20,000 IU to 3600,000 IU in pediatric subjects and 200,000 IU to 96,00,000 IU in adults. CONCLUSIONS: Supplementation is a leading cause of potential toxic levels of 25OHD. The condition can be prevented by careful use of VD supplements and consistent monitoring.

Effect of physical activity and vitamin D compared with vitamin D alone on muscle strength, back flexibility and aerobic activity in patients with chronic kidney disease: A comparative study from Pakistan.

BACKGROUND AND OBJECTIVES: To compare the differences in musculoskeletal health with vitamin D alone in comparison with vitamin D with physical activity (PA) among chronic kidney disease (CKD) patients. METHODS AND STUDY DESIGN: An open labeled, randomized, controlled trial was conducted at two tertiary care centers in Pakistan. Patients with CKD stage 2-4 and vitamin D deficiency (<20 ng/mL) were recruited in the trial. Both the arms were given oral vitamin D (cholecalciferol) drops (4000 IU) once daily for three months. One arm received only vitamin D (VD arm), while the second arm received vitamin D along with PA (VDPA arm). RESULTS: Of the 1,235 CKD stage 2-4 subjects contacted, forty-six subjects were enrolled. Eighteen were assigned to VD arm and twenty-eight were assigned to VDPA arm. Between groups comparison shows that bicep strength increases from 15 to 17 kg. Likewise, back flexibility and aerobic fitness also increased among those who receive vitamin D and physical activity, however these differences were not statistically significant (p>0.05). Sensitivity analysis within group comparison shows rise of bicep strength from 13.8 kg to 15.2 kg in the VD alone arm (p=0.05); however, in the VDPA arm, there is a greater difference of 14.3 kg to 17.2 kg (p<0.001). CONCLUSIONS: Targeted PA among CKD patients has potential to improve bicep strength and back flexibility. However, as the sample size was small, further studies would be required to suggest whether a PA should be included as part of the treatment regimen.

Bridging the gaps in secondary fracture prevention at a single center in Pakistan-compliance with the IOF best practice framework.

PURPOSE: The International Osteoporosis Foundation (IOF) formulated a set of best practice framework as an international benchmark for secondary fracture prevention (SFP) and fracture liaison services (FLS), delineating essential elements of service delivery. The aim of this audit was to assess compliance with the IOF standards for patients ≥ 50 years presenting with fragility hip fractures at a tertiary care center in Pakistan. METHODS: A retrospective sample of hip fracture cases from Jan 2019 to Dec 2019, treated at the section of Orthopedic Surgery, Aga Khan University, Karachi, was conducted. After excluding high energy trauma cases and patients younger than 50 years of age, medical records were audited, using a pre-structured Performa based on IOF standards. Compliance level of 0, 1, 2, and 3 was recorded as defined by IOF. Microsoft excel was used for data analysis. RESULTS: A compliance level of 3 was recorded for patient identification and fall prevention services, whereas level 1 was attained for database maintenance for 25 (100%) cases. For medication initiation, level 0 was recorded for all the cases; however, 8 (32%) cases were prescribed calcium and vitamin D supplements. For the standards, including post-fracture assessment timing, evaluation of secondary causes of osteoporosis, multifaceted assessment, medication review, communication strategy, and long-term management, a level 0 was noted for 25 (100%) cases. Moreover, no recommended assessment guidelines were followed uniformly. CONCLUSION: The care gaps identified require substantial efforts to ensure adequate implementation of the overall best practice standards for SFP, necessitating the need for FLS initiation and establishment of fracture care pathway.

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan.

ABSTRACTINTRODUCTIONANDIMPORTANCE: Autosomal dominant hypophosphatemic rickets is the most common form of rare rickets, commonly manifests in children but sometimes the condition remains undiagnosed due to lack of knowledge &/or awareness of treating physicians or surgeons. CASE PRESENTATION: We describe a case of 43 years old female with multiple fragility fractures since childhood, corrected surgically but never investigated. She had stunted growth, bowing deformities and loss of teeth. CLINICAL DISCUSSION: A detailed history and examination along with metabolic and genetic work up mounted the diagnosis of X linked hypophosphatemic osteomalacia. The pathophysiology involves the mutation or the loss of the phosphate regulating gene on PHEX, that causes reduced mineralization of bones and teeth. CONCLUSION: Diagnostic delay in this patient resulted in increased disabilities affecting her mobility and lif estyle.

Exit sites on the epicardium rarely subtend critical diastolic path of ischemic VT on the endocardium: Implications for noninvasive ablation.

BACKGROUND: Noninvasive electrocardiographic mapping of ventricular tachycardia (VT) and ablation using stereotactic radiotherapy was recently reported. This strategy does not directly evaluate the critical diastolic components and assumes that the epicardial exit site of VT subtends closely over the endocardial mid-diastolic isthmus. OBJECTIVE: To determine if the epicardial exit site of VT spatially corresponds to the critical diastolic components of ischemic scar-related VT. MATERIALS AND METHODS: Intraoperative simultaneous endocardial and epicardial mapping were performed during VT using a 112-bipole endocardial balloon and 112-bipole epicardial sock array. In eight patients, nine VTs having entire diastolic circuit mapped were included in the study. The diastolic path and VT-exit sites (epicardial and endocardial) were determined. RESULTS: The diastolic path was mapped in the endocardium for all nine VTs (median length, 50; interquartile range [IQR], 28 mm). The tachycardia cycle length ranged from 210-500 ms. The VT-exit site was early in the endocardium for six VTs and on the epicardium for three VTs. The mid-diastolic isthmus and endocardial exit site of the six endocardial VTs were spatially distant from their epicardial exit site by a median distance of 32 and 27 mm, respectively. For the three VTs with an early epicardial exit, the isthmus and endocardial exit sites were distant from the epicardial exit site by a median distance of 34 and 38 mm, respectively. CONCLUSION: The epicardial exit site and the mid-diastolic isthmus sites were spatially distant and discrepant. Surface electrocardiography (ECG)-derived strategy in identifying epicardial exit site to select noninvasive ablation targets is prone to identify epicardial exit sites and may not identify critical targets in ischemic scar VT.