Platelet Count to Prothrombin Time: A Noninvasive Predictor of Esophageal Varices in Patients With Chronic Liver Disease.

Introduction Esophageal variceal bleeding is a potentially deadly consequence of portal hypertension in patients with cirrhosis. Although upper gastrointestinal endoscopy is still the preferred method for identifying esophageal varices (EV), the present study measured the platelet count to prothrombin time (PLT/PT) ratio for the assessment of portal hypertension and subsequent diagnosis of EVs in patients with chronic liver disease (CLD). Methods This was an observational comparative study conducted in the outpatient department of Patel Hospital, Karachi, Pakistan, using a non-probability consecutive sampling technique. Ethical approval was obtained from the Patel Hospital ethical review committee (PH/IRB/2022/028). An independent sample t-test was used for parametric data, whereas the Mann-Whitney U test was used for non-parametric data. The chi-square test was used to compare the categorical data of patients with and without EV. Receiver operating characteristic (ROC) analysis was performed to evaluate the cutoff values for the PLT/PT ratio, sensitivity, specificity, and area under the curve (AUC). Results The study involved 105 patients with and without EV. Among them, 38 (63.3%) males and 22 (36.7%) females had EV, whereas 30 (66.7%) males and 15 (33.3%) females did not. The platelet (PLT) count was also significantly lower in patients with EV (87.6 ± 59.8) than in those without (176.6 ± 87.7) (p < 0.001). The PLT/PT ratio was significantly lower in patients with EV (median: 5.04, IQR: 3.12-9.21) compared to those without (median: 14.57, IQR: 8.08-20.58) (p < 0.001). The sensitivity and specificity of the PLT/PT ratio for identifying EVs were 97.80% and 83.30%, respectively. Conclusion We found a significantly lower PLT/PT ratio in cases with EV than those without EV. After defining an optimal cutoff, PLT/PT had a high sensitivity in identifying cases with EVs in CLD. Therefore, we conclude that in patients with CLD, the PLT/PT ratio is a noninvasive predictor for the presence of EV.

Correlation of Serum Sodium and Potassium With Thiamin Levels in Type 1 and Type 2 Diabetic Patients.

Introduction Chronic metabolic disorders such as diabetes mellitus (DM) are becoming a global health concern. According to recent studies, the pathophysiology of DM may involve factors other than traditional glycemic control, such as electrolyte balance and thiamin status. Therefore, this study evaluated the relationship between sodium and potassium and serum thiamin levels in patients with type 1 and type 2 DM. Methods This study was conducted in multiple diabetic outpatient clinics and centers in Karachi, Pakistan, using a non-probability convenience sampling method. The study lasted for approximately six months after the synopsis was approved. A total of 64 patients were selected, 32 of whom each had type 1 and type 2 DM. All patients who were between the ages of 25 and 46 years old and had either type 1 or type 2 DM were included in the study. A Mann-Whitney test and an independent t-test were used to compare the means between the two study groups. Pearson's correlation and chi-square tests were used to determine the variables, correlations, and associations with type 1 and type 2 DM. Results The study findings showed that the distribution of gender among diabetic patients revealed that among males, eight (25.0%) had type 1 DM, and 10 (31.2%) had type 2 DM. Among females, 24 (75.0%) had type 1 DM, and 22 (68.8%) had type 2 DM. Significant correlations were observed in the means of blood glucose levels, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and serum thiamin levels, among patients with type 1 and type 2 DM (p < 0.001). The HbA1c, FBS, and serum thiamin levels were significantly higher in type 2 DM patients than in type 1 DM patients. Among patients with type 1 DM, sodium levels were not substantially correlated with thiamin levels (p = 0.570, r = 0.104), whereas potassium levels were significantly correlated with thiamin levels (p = 0.005, r = 0.263). Conclusion We conclude that the sodium level was not significantly correlated with serum thiamin status in type 1 and type 2 DM, whereas a low positive correlation was observed between potassium and serum thiamin levels in type 1 DM. However, there was no significant correlation concerning potassium levels in type 2 DM.

Serum Vitamin B12 Deficiency in Chronic Hemodialysis Patients.

Introduction Essential vitamins like folate and vitamin B12 are crucial for many physiological functions. Patients with renal failure undergoing regular hemodialysis in the general population may experience harmful effects from vitamin B12 deficits. Therefore, this study aimed to determine the frequency of vitamin B12 deficiency in hemodialysis patients and its association with other clinical parameters. Methods This cross-sectional study was conducted at the dialysis unit of Patel Hospital and Lifeline Hospital, Karachi, using a non-probability consecutive sampling technique after obtaining ethical approval from Lifeline Hospital (LLH/HR/02-22). The study duration was six months, from January 10, 2023, to July 22, 2023. A total of 135 adult renal failure patients with ages >18 and <70 years on maintenance hemodialysis for >1 year were included in the study. The chi-square test was used to determine the association between vitamin B12 deficiency and age and gender. A p-value of 0.05 was considered statistically significant. Results The study findings showed that out of 135 patients, 82 (60.7%) were males and 53 (39.3%) were females, with a mean age of 50.80 ± 10.03 years. The duration of hemodialysis was approximately 1-2 years in 98 (72.6%) patients, 2-3 years in 27 (20.0%) patients, and 3-4 years in only 9 (6.7%) patients. The mean serum vitamin B-12 levels were 411.61 ± 224.95 pg/ml, with 30 (22.2%) of the subjects being deficient. In terms of duration of hemodialysis, there was a significant association (p= 0.013). Between patients with normal 4 (4%) and deficient 5 (17%) vitamin B12 and 3-4 years of hemodialysis. Conclusion In this study, we found that a significant proportion of patients on chronic hemodialysis had vitamin B12 deficiency. Moreover, vitamin B12 deficiency was significantly associated with duration of hemodialysis. Therefore, we recommend periodic vitamin B12 testing in hemodialysis patients to avoid any associated complications.

Frequency and Types of Anemia in Primary Hypothyroidism Patients: A Prospective Observational Study.

Background Primary hypothyroidism is a common endocrine disorder resulting from inadequate production of thyroid hormones. Anemia is a common condition that can occur in hypothyroidism. Anemia may occur due to nutrient deficiency, such as iron or vitamin B12 deficiency due to chronic disease in hypothyroidism. Therefore, it is important to evaluate the cause of anemia in hypothyroidism.  Objective The aim of this study was to determine the frequency of anemia and its types in patients with primary hypothyroidism. Methods This was a prospective cross-sectional observational study conducted at the Department of Medicine, Jinnah Postgraduate Medical Center, Karachi, Pakistan, using non-probability consecutive sampling. A total of 176 adults aged 18-65 years of either gender, newly diagnosed with primary hypothyroidism, or with any of its symptoms were included in the study. Patients already on anti-thyroid medication and with post-thyroidectomy hypothyroidism were excluded from the study. The duration of the study was 1.5 years, from January 2020 to July 2021. After ethical approval, written informed consent was obtained from each patient. Demographical data along with results of complete blood picture, including Hb and MCV for diagnosing anemia and its types were recorded on a pre-designed proforma. The chi-square test was applied keeping p < 0.05 as statistically significant. Results The mean age of the patients was 42.19 ± 8.43 years, with 59.66% (n = 105) females and 40.34% (n = 71) males. A total of 67% (n =118) patients were found to be anemic. Of these, 38.64% (n = 68) patients had normocytic anemia, 19.32% (n = 34) microcytic anemia, and 9.25% (n = 16) patients had macrocytic anemia; 56.34% (n = 40) males and 74.29% (n = 78) females were reported to be anemic (p = 0.01). Conclusion In our study, the frequency of anemia in patients with hypothyroidism was high, with normocytic anemia being the most common type. It is important to know the type of anemia in hypothyroidism, as normocytic anemia is due to the chronic disease process (anemia of chronic disease) and may not respond to nutrient supplementation. Conversely, microcytic anemia is commonly due to iron deficiency and macrocytic anemia is due to vitamin B12 deficiency and therefore, they require replacement therapy. In any case, it is important to identify and treat the underlying cause of anemia.

Correlation of Blood Urea and Creatinine Levels With Thiamin Levels in Type 1 and Type 2 Diabetic Patients.

Introduction Serum urea and creatinine levels are the most commonly recognized parameters for evaluating renal impairment in patients with diabetes mellitus (DM). Therefore, this study evaluated the correlation between urea and creatinine levels and thiamin levels in patients with type 1 DM (T1DM) and type 2 DM (T2DM). Methods This multi-center, cross-sectional study was conducted at diabetic outpatient clinics in Karachi. The duration of the study was six months, from 1st January 2023 to 30th June 2023. A total of 60 patients were enrolled and divided into two groups, i.e., T1DM and T2DM, each containing 30 patients of both genders between the ages of 24 and 42 years. Demographic data and biochemical variables, such as urea, creatinine, random blood sugar, fasting blood sugar, hemoglobin A1c, and serum thiamin levels, were assessed. The Mann-Whitney U test and independent t-test were used to associate the means between the two study groups. The chi-square test and Spearman's correlation coefficient were used to determine the associations between the variables and T1DM and T2DM. Results The study results revealed that patients with T2DM had a significantly higher frequency of hypertension (p = 0.039), neuropathy (p = 0.038), and coronary artery disease (p = 0.010) than those with T1DM, in both genders. The level of serum thiamin was found to be significantly higher (p < 0.001) in T2DM (14.8 ± 4.82) than in T1DM patients (7.34 ± 1.90). Similarly, serum creatinine was higher in T2DM than in T1DM patients (0.83 ± 0.12 vs. 0.76 ± 0.17, p = 0.025). Moreover, the correlation of urea and creatinine with thiamin levels in T1DM and T2DM patients revealed that in T1DM and T2DM patients, urea and creatinine showed an insignificant positive correlation with thiamin levels. Conclusion We found a significantly higher level of serum creatinine and thiamin levels in T2DM patients than in T1DM; however, there was no significant correlation between urea and creatinine levels and thiamin status in T1DM and T2DM patients. Therefore, we conclude that although serum urea, creatinine, and serum thiamin are important disease biomarkers in diabetic patients, there is no correlation between them.

AstraZeneca COVID-19 Vaccine and Diabetes Mellitus: A Prospective Clinical Study Regarding Vaccine Side Effects.

Background Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide, and vaccination is currently the most effective way to control its spread and reduce its severity. Diabetes mellitus (DM) is a prevalent chronic disease that poses a significant health risk and is a frequent comorbidity in COVID-19 patients. Therefore, this study aimed to assess the frequency of local and systemic side effects of the AstraZeneca vaccine among diabetic and non-diabetic participants. Methodology This multicenter study was designed as a cross-sectional prospective study and was conducted in Pakistan using a non-probability consecutive sampling method. The study duration was eight months from August 1, 2022, to March 31, 2023. A total of 700 participants who received both (first and second) doses of the AstraZeneca immunization were included in the study. An independent t-test was applied to determine the association between the means and standard deviations of age, height, weight, and duration of DM and hypertension. The chi-square test was used to evaluate the association between local and systemic side effects. Results Among the 700 participants, 173 (49.4%) males and 177 (50.6%) females had diabetes, whereas 183 (52.3%) males and 167 (47.7%) females did not have DM; their mean ages were 46.95 ± 12.73 years (diabetics) and 38.10 ± 14.14 years (non-diabetics). The most frequent adverse effects of the AstraZeneca vaccine after the first dose were pain at the injection site, reported by 259 (74.0%) diabetics and 226 (64.6%) non-diabetic participants; however, after the second dose, injection site swelling in 170 (48.6%) diabetic and 163 (46.6%) non-diabetic recipients was the most commonly reported local side effects. Conclusions This study concluded that concurrent medical conditions such as DM had substantially more local and systemic side effects than those without the disease. After receiving both doses of the AstraZeneca vaccine, the most frequently reported local side effects in both diabetic and non-diabetic participants were pain, swelling, and burning at the injection site, followed by systemic side effects such as fever.

Association Between Pfizer COVID-19 Vaccine Adverse Effects and Diabetes Mellitus: A Prospective Multicenter Study.

Introduction The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the contagion of coronavirus disease 2019 (COVID-19), which killed many individuals globally. The Pfizer BioNTech vaccine was the first messenger ribonucleic acid (mRNA)-based vaccine that boosted immunity against various adverse reactions. The objective of this study was to evaluate the frequency of Pfizer vaccine side effects among participants with and without diabetes mellitus (DM). Methods This multicenter study was cross-sectional and was performed using a non-probability consecutive sampling technique. The study duration was six months, from October 1, 2022, to March 31, 2023. A total of 750 participants who received both doses of the Pfizer vaccine were included in the study. Demographic details such as gender, age, comorbidities, preceding COVID-19 infection, and the occurrence of any local and systemic side effects of the first and second doses of vaccine were recorded. The association between local and general side effects and the presence of DM was assessed using the chi-square test. Results Of the 750 participants included in the study, 289 (77.1%) were males with diabetes mellitus (DM), and 217 (57.9%) were non-diabetic participants; however, 86 (22.9%) females had DM, and 158 (42.1%) were non-diabetic; their mean ages were 48.23 ± 16.22 and 37.56 ± 12.15 years, respectively. The most commonly occurring side effects after receiving the first dose of the Pfizer vaccine were: injection site burning in 251 (66.9%) diabetic and 254 (67.7%) non-diabetic participants. Likewise, the frequency of side effects of the second dose of the Pfizer vaccine showed that the most commonly reported side effects were: muscle pain, found in 240 (64.0%) diabetic patients and 194 (51.7%) non-diabetics, with a statistically significant association (p =0.001). Conclusion This study concluded that participants with DM had local and general adverse effects considerably more frequently than those without DM. The most frequently observed adverse effects in both diabetic and non-diabetic participants were injection site burning, rashes, muscle pain, and fever after receiving both doses of the Pfizer vaccine. Moreover, most of the side effects were minor.

Prevalence of Side Effects of the AstraZeneca COVID-19 Vaccine: A Multicenter Experience From Pakistan.

Introduction The most efficient method of combating the coronavirus disease 2019 (COVID-19) pandemic would be to use effective, safe, and proven vaccines; however, their widespread use has been hampered partly by concerns over possible adverse effects. Therefore, this study aimed to assess the prevalence of Oxford/AstraZeneca vaccine side effects among participants. Methods This was a multicenter, cross-sectional study conducted using a non-probability sampling technique. The duration of the study was nine months, from February 1, 2022, to October 31, 2022. The study included 900 participants who provided informed consent and had received two doses of the AstraZeneca vaccine. Demographic characteristics of participants, such as gender, age, comorbidities, AstraZeneca vaccine with both doses along with booster dose, previous exposure to COVID-19 infection, and the prevalence of any local and systemic side effects following the first and second doses of vaccine, were documented. Results The study findings showed that of the 900 participants, 414 (46.0%) were males and 486 (54.0%) were females; their mean age was 40.72 ± 13.47 years. Among them, 198 (22.0%) had hypertension and 144 (16.0%) had diabetes mellitus. Following the first dose of the AstraZeneca vaccine, pain at the injection site was the most commonly reported side effect in 594 (66.0%) participants. Moreover, swelling at the injection site was the most commonly reported side effect in 522 (58.0%) participants after receiving the second dose of the vaccine. The level of satisfaction showed that the majority of the 648 participants (72.0%) were satisfied with their vaccination. Conclusion This study concluded that pain at the injection site was the most commonly reported side effect, followed by swelling and fever after the first dose of the vaccine. Following the second dose of the vaccine, adverse effects included headache, swelling, and burning at the injection site.

Severity of Adverse Effects of Sinovac COVID-19 Vaccine in Postmenopausal Women: A Multicenter Experience From Pakistan.

Introduction The most significant element in halting the coronavirus disease 2019 (COVID-19) epidemic was the availability of reliable and efficient vaccines. Vaccine acceptability is influenced by many factors, including perceptions of the vaccine's safety and side effects. Adverse reactions to vaccines can vary with regard to the type, although they are frequently mild, localized, temporary, and self-limiting. Therefore, this study aimed to assess the prevalence of side effects experienced by postmenopausal women after receiving the Sinovac vaccine. Methods This multicenter, prospective cross-sectional study was carried out at multiple centers in Karachi, Pakistan. In this study, the non-probability sampling method was used. The study continued from August 1, 2022, to January 31, 2023, for six months. The study comprised 600 postmenopausal women over the age of 50 years who received two doses of Sinovac COVID-19 vaccination. Demographic parameters such as gender, the existence of comorbidities, and local and systemic side effects in postmenopausal women were documented as frequencies and percentages. Age, weight, and duration of comorbidities are expressed as means and standard deviations. Results The study findings showed that the mean age of study participants was 63.93 ± 8.24 years. There were related comorbidities with hypertension and diabetes mellitus in 181 (30.2%) and 40 (6.7%) women, respectively. Fever was the most often reported side effect, with 349 (58.2%) participants reporting it and 198 (56.7%) participants reporting it as mild. After the second dose, 234 (39.5%) participants reported fever as their most frequent adverse effect, and 158 (67.5%) of them reported it was mild. Conclusion This study concluded that the most commonly reported side effects among postmenopausal women were fever, pain, and swelling at the injection site after getting either dose of Sinovac vaccine. These overall side effects were generally mild to moderate in intensity, not life-threatening, and did not require hospitalization, although fever was reported in severe intensity in some cases, particularly after the first dose.

Clinicopathological Parameters Predicting Malignancy in Phyllodes Tumor of the Breast.

Introduction Phyllodes tumor (PT) is an uncommon fibroepithelial neoplasm of the breast. It is a biphasic tumor with stromal and epithelial components, with a tendency to recur. Because of its wide range of disease manifestations, it has been subclassified into three categories, i.e., benign, borderline, and malignant, based on several histological parameters. This study was conducted to evaluate the clinicopathological features associated with malignancy in breast PTs. Methods We conducted a retrospective study at the Department of Histopathology at Liaquat National Hospital, Karachi, Pakistan. A total of 146 biopsy-proven cases of PTs were enrolled in the study. Clinical data were obtained from the clinical referral forms. Specimens were obtained from either lumpectomy or simple mastectomy. The specimens obtained were received at the laboratory where after gross examination, paraffin-embedded tissue blocks were prepared, which were sectioned, stained, and studied by a senior histopathologist. Pathological features, such as mitotic count, necrosis, stromal atypia, stromal overgrowth, and heterologous elements, were observed. Based on these features, the PTs were classified into benign, borderline, and malignant tumors. Results The mean age of the PTs in our setup was 40.65 ± 12.17 years with a mean size of 9.40 ± 6.49 cm. Malignant PT was found to be the most prevalent in our population, accounting for 63 (43.2%) cases, followed by borderline (51, 34.9%) and benign (32, 21.9%). A significant association was found between the tumor subtype and patient age, i.e., patients diagnosed with malignant and borderline PTs were found to be of older age (mean 42.82 ± 12.94 and 42.05 ± 11.31 years, respectively) than those diagnosed with benign PTs (mean age 34.12 ± 9.75 years). Moreover, malignant PTs were associated with larger tumor size (mean 11.46 ± 6.08) compared with the other two subtypes. Conclusion We found a significant association among patient age, tumor size, and PT subtype. Therefore, apart from the usual histological parameters, patient age and tumor size are important parameters for predicting the behavior of breast PT and should be considered for management.

CanSino COVID-19 Vaccine: Comparison of Vaccine Adverse Effects Among Diabetic and Non-diabetic Recipients.

Introduction The emergence of potent vaccines is crucial in the fight against the coronavirus disease 2019 (COVID-19) pandemic. Two of the many factors influencing the acceptance of the vaccine are perceptions about its efficacy, effectiveness, safety, and side effects. Thus, this study compared patients with and without diabetes mellitus (DM) who received the CanSino (CanSinoBIO, Tianjin, China) COVID-19 vaccination to identify the prevalence of local and general side effects. Methods This was a multicenter, cross-sectional study performed using a non-probability sampling method. The study period was six months, from August 1, 2022, to January 31, 2023. The study included 600 participants who provided informed consent and had received the CanSino vaccine in a single dose. Demographic characteristics of the participants, including gender, age, weight, and height; comorbidities such as hypertension and diabetes; previous infection with COVID-19; and the prevalence of any local and systemic side effects following vaccination, were documented. Between diabetic and non-diabetic participants, the relationship between local and general side effects and satisfaction levels was assessed using the chi-square test. Results The study findings showed that out of 600 participants, 287 (95.7%) were males and 13 (4.3%) were females who had DM, whereas 229 (76.3%) males and 71 (23.7%) females did not. There was a statistically significant association between the two groups (p < 0.001). After receiving a single dose of the CanSino vaccine, the most frequently noticeable side effect was fever, which was noticed in 260 (86.75%) diabetic patients and 279 (93.0%) non-diabetic participants, with a significant association noted among them (p=0.010). Among the non-diabetic participants, 164 (54.7%) were satisfied, and 155 (51.7%) diabetics and 65 (21.7%) non-diabetic participants were extremely pleased with their vaccinations. Conclusion This study concluded that participants with comorbid diseases such as DM had both general and local side effects far more frequently than those without DM. The most noticeable side effects after a single dose of CanSino were fever, injection site pain, and burning. The CanSino vaccine did not require hospitalization and had a relatively low frequency of local and systemic side effects.

Correlation of Fasting Blood Sugar and Glycated Hemoglobin (HbA1c) With Thiamine Levels in Diabetic Patients.

Introduction It has been discovered that low levels of thiamine reserves in the body are related to diabetes mellitus (DM) because thiamine directly influences carbohydrate metabolism. Therefore, the purpose of this study was to assess several metabolic variables and blood thiamine levels in patients with type 1 and type 2 DM and compare them with those in a control group of healthy individuals. Methods This case-control study was conducted at multiple diabetic outpatient centers in Karachi. A total of 90 participants, who were divided into three groups, each containing 30 individuals, were chosen using a convenient non-probability sampling technique. Group A served as the control group and consisted of healthy, non-diabetic individuals. Groups B and C contained subjects with type 1 and type 2 DM, respectively. Descriptive analysis was reported as mean standard deviation, whereas gender and comorbidities were expressed as frequencies and percentages. The chi-square test and Pearson's correlation coefficient were used to determine the associations of the variables with type 1 DM, type 2 DM, and controls. Results The study results revealed statistically significant differences between controls, type 1 and type 2 DM, in the means of blood glucose levels and all lipid profiles, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), random blood sugar (RBS), serum thiamine, triglycerides (p < 0.001), high-density lipoprotein (HDL) (p = 0.014), and total cholesterol (p = 0.013). Furthermore, it was shown that among the control group, type 1 and type 2 DM, HbA1c, and FBS were insignificantly correlated with thiamine levels, whereas the HbA1c and FBS of the combined diabetic groups were significantly correlated with the thiamine level (r = 0.465, p < 0.001) and (r = 0.360, p = 0.005), respectively, where 'r' is the Pearson correlation coefficient. Additionally, HbA1c and FBS in the combined three groups were significantly correlated with the thiamine level (r = -0.626, p < 0.001) and (r = -0.561, p < 0.001), respectively. Conclusion This study concluded that patients with type 1 and type 2 DM had significantly higher levels of FBS, RBS, HbA1c, triglycerides, and total cholesterol than controls. Furthermore, both type 1 and type 2 DM patients' serum thiamine and HDL levels were observed to be considerably lower than those of controls. Additionally, among both types of DM and controls, there was a strong correlation between FBS and HbA1c. Therefore, we recommend that serum thiamine levels be routinely monitored in diabetic patients, and thiamine supplementation should be considered to avoid complications, especially vascular complications of DM.

Mismatch Repair Deficient (dMMR) Colorectal Carcinoma in a Pakistani Cohort: Association With Clinical and Pathological Parameters.

Introduction Microsatellite instability (MSI) is an important pathway in colorectal carcinoma (CRC) pathogenesis. MSI occurs due to mutations in mismatch repair (MMR) genes that include MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6). CRC with MSI is termed MMR deficient (dMMR) CRC. Conversely, CRC with intact MMR genes is called microsatellite stable (MSS) or MMR proficient (pMMR). In this study, we compared the clinicopathological features of dMMR CRC with pMMR CRC. Methods It was a retrospective study conducted in the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, from March 2020 to February 2022, over a duration of two years. Biopsy-proven cases of CRC with upfront surgical resection were included in the study. Microscopic examination was performed to evaluate tumor type, grade, and extent of invasion, presence of necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), peritumoral lymphocytes (PTL), intratumoral lymphocytes (ITL), and nodal metastasis. Immunohistochemical staining was performed using antibodies, namely, MLH1, PMS2, MSH2, and MSH6. Any loss of nuclear expression in tumor cells was termed dMMR or microsatellite instable, whereas the intact nuclear expression in tumor cells was labeled as MSS or pMMR. Results A total of 135 cases of CRC were included in the study. The mean age at diagnosis was 46.76 ± 17.74 years, with female predominance (60.7%). The loss of MLH1, PMS2, MSH2, and MSH6 expression was noted in 39.3%, 34.1%, 17.8%, and 16.3% cases, respectively. Overall, 59.3% of CRCs were pMMR, while 40.7% were dMMR. A significant association of MMR status was noted with respect to age, PNI, LVI, tumor grade, tumor (T) and nodal (N) stage, mucinous differentiation, and ITL. dMMR CRC was significantly above 50 years than pMMR CRC. The frequency of PNI and LVI was lower in dMMR CRC than in pMMR CRC. Conversely, the higher grade (grade 3) and higher T-stage (T4) were associated with dMMR CRC. Alternatively, the frequency of higher N stage (N2b) was more commonly seen in pMMR CRC. Moreover, mucinous differentiation and ITL were significantly associated with dMMR CRC. Conclusion A significant proportion of CRC patients in our population demonstrated dMMR status. dMMR CRC had a higher histological grade with a higher frequency of mucinous differentiation and higher T-stage. Conversely, the presence of LVI, PNI, and higher N stages were associated with pMMR CRC.

Early-Onset/Young-Onset Colorectal Carcinoma: A Comparative Analysis of Morphological Features and Biomarker Profile.

Introduction Colorectal carcinoma (CRC) is one of the most common cancers that involve the human body. Young-onset CRC (YO-CRC) or early-onset CRC (EO-CRC) is defined as CRC that develops before the age of 50 years, as opposed to CRC that is diagnosed after the age of 50, referred to as late-onset CRC (LO-CRC). EO-CRC is sparsely studied in our population. Therefore, in this study, we evaluated the clinicopathological parameters and biomarker profile of EO-CRC and compared them with those of LO-CRC. Methods This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan. A total of 254 biopsy-proven cases of CRC, reported over a period of nine years, were enrolled in the study. The specimens collected during surgery were sent to the laboratory for histopathological and immunohistochemical (IHC) status examinations. IHC staining of the specimens was performed using antibodies, namely, MutL protein homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and human epidermal growth factor receptor 2 (HER2/neu), on representative tissue blocks. A comparison of morphological and biomarker profiles between EO-CRC and LO-CRC was performed. Results The mean age at diagnosis was 46.27±17.75 years, with female predominance (59.8%). A significant difference between the two groups (EO-CRC and LO-CRC) was noted with respect to laterality, tumor site, tumor grade, tumor type, presence of pre-existing polyps, perineural invasion (PNI), lymphovascular invasion (LVI), and IHC markers. EO-CRC (as opposed to LO-CRC) significantly affected the left colon (92.6% vs. 72.9%, p<0.001), with the rectosigmoid being the most common site in the majority of cases (72.1% in EO-CRC vs. 61% in LO-CRC). EO-CRC showed a higher frequency of PNI and LVI than LO-CRC (42.6% vs. 23.7%, p=0.001; 29.4% vs. 18.6%, p=0.046, respectively). A significantly higher proportion of EO-CRCs were mucinous (42.6%) and medullary carcinoma (11.8%). Although the majority (54.4%) of cases of EO-CRC were grade 2 tumors at the time of diagnosis, a significantly higher proportion of them were grade 3 (44.1%) compared with LO-CRC. IHC comparisons between the two age groups showed that a significantly higher proportion of cases of EO-CRC showed positive HER2/neu expression (27.1%) compared with LO-CRC (13.2%). Conversely, the loss of expression of microsatellite instability (MSI) markers was more commonly seen in LO-CRS compared with EO-CRC. Conclusions We found a relatively higher frequency of EO-CRC in our population. Moreover, compared with LO-CRCs, EO-CRCs were associated with prognostically poor histological parameters, such as mucinous and medullary carcinoma, high-grade, PNI, and LVI. Similarly, EO-CRC had a higher positive expression of HER2/neu with intact MSI markers compared with AO-CRC; all these characteristics indicate poor biological behavior in EO-CRC.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

INTRODUCTION:  Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC). Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters. METHODS:  This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought. RESULTS:  p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression. CONCLUSION:  Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features.

Luminal B, Human Epidermal Growth Factor Receptor 2 (HER2/neu), and Triple-Negative Breast Cancers Associated With a Better Chemotherapy Response Than Luminal A Breast Cancers in Postneoadjuvant Settings.

Background Breast cancer is a heterogeneous disease with many histological and molecular/intrinsic breast cancer subtypes. Intrinsic breast cancer subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2/neu), and triple-negative subtypes. The intrinsic breast cancer typing is based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, and Ki67-labeling index. One of these patients' foremost prognostic factors upon surgical resection is a response to neoadjuvant chemotherapy. The presence of a pathologically complete response (pCR) indicates a favorable patient outcome compared with a pathologically partial response (pPR). In this study, we compared the neoadjuvant chemotherapy response in breast cancer in different intrinsic breast cancer subtypes. Methodology It was a retrospective cross-sectional study conducted in the Department of Histopathology, Liaquat National Hospital, from January 2019 to December 2022, over three years. A total of 287 post-neoadjuvant chemotherapy cases of breast cancer were included. Anthracyclines and taxanes, coupled with or without anti-HER2/neu therapy, have been used in the neoadjuvant chemotherapy treatment setting contingent upon the patients' HER2/neu status. The post-chemotherapy response was assessed pathologically and categorized into pCR and pPR. Results The mean age of the patients was 47.90 ± 10.34 years, with a mean tumor size and Ki67 index of 5.36 ± 2.59 cm and 36.30 ± 22.14%, respectively. Invasive breast carcinoma of no special type (IBC-NST) made up 88.2% of cases, while grade 2 carcinomas made up 45.5%. The majority of tumors (42.7%) belonged to tumor (T) stage T2, and nodal metastasis was detected in 59.7% of patients. The intrinsic breast cancer subtypes luminal B (40.6%) and triple negative (33.3%) were the most prevalent, followed by luminal A (15.8%) and HER2/neu (10.3%). In 81 cases (24.5%), pCR was detected. The association of post-neoadjuvant chemotherapy response with intrinsic breast cancer subtypes showed a significant difference (P < 0.001). The highest frequency of pCR was noted in HER2/neu cancers (58.8%), followed by luminal B (25.4%) and triple negative (23.6%). Regarding age, T-stage, tumor grade, and histological type of carcinoma, there was no discernible difference between pCR and pPR. Conversely, a significant association was noted for the Ki67 index. A Ki67 index higher than 25% showed a significantly higher frequency of pCR. Conclusions In postchemotherapy specimens, the HER2/neu breast cancer subtype substantially displayed higher pCR, followed by luminal B and triple-negative subtypes. After identifying the patients' subtypes, intrinsic subtyping can help determine the prognosis and anticipated response to chemotherapy. Furthermore, prechemotherapy breast specimens with high Ki67 index values have shown a direct association with neoadjuvant chemotherapy response.

Neurological Features and Their Association With Gender in Diabetes Mellitus Patients.

Introduction Understanding the wide range of clinical signs and symptoms associated with diabetes mellitus (DM) is crucial because people with DM are frequently misdiagnosed, given incorrect care, or poorly controlled. Therefore, the purpose of this study was to evaluate the neurological symptoms associated with type 1 and type 2 DM patients with respect to patient gender. Methods This was a cross-sectional multicenter study that was conducted at different hospitals using a non-probability sampling method. The duration of the study was eight months, from January 2022 to August 2022. The study involved 525 type 1 and type 2 DM patients with an age range from 35 to 70 years. Demographic details such as age, gender, socioeconomic status, past medical history, presence of comorbidities, type, and duration of DM, and neurological features were recorded as frequencies and percentages. A Chi-square test was used to determine the association between neurological symptoms associated with type 1 and type 2 DM and gender. Results The study findings showed that of 525 diabetic patients, 210 (40.0%) were females and 315 (60.0%) were males. The mean male and female mean ages were 57.36±14.99 and 50.52±14.8 years, respectively, with a significant difference with respect to gender (p<0.001). The prevalence of neurological manifestations showed that irritability or mood swings were reported by most of the male 216 (68.6%) and 163 (77.6%) female diabetic patients, with a significant association noticed (p=0.022). Moreover, a significant association was observed between both genders in terms of swelling of feet, ankles, hands, and eyes (p=0.042), confusion or difficulty in concentration (p=0.040), burning pain in feet or legs (p=0.012), and muscular pain or cramps in legs or feet (p=0.016).  Conclusion This study concluded that the prevalence of neurological manifestations was high among diabetic patients. Most of the neurological symptoms were significantly more pronounced in female diabetic patients. Moreover, most of the neurological symptoms were associated with the type (type 2 DM) and duration of DM. The presence of hypertension, dyslipidemia, and smoking also influenced some neurological manifestations.

Clinicopathological Parameters Predicting Nodal Metastasis in Head and Neck Squamous Cell Carcinoma.

Introduction Squamous cell carcinoma (SCC) is the most common type of malignancy of the head and neck region arising from the mucosal epithelium of the oral cavity and oropharynx. It is a multifactorial disease with a high rate of mortality. Lymph node metastasis is an important prognostic parameter associated with adverse prognosis. This study was conducted to establish a relationship between various clinicopathological characteristics and nodal metastasis in head and neck squamous cell carcinoma (HNSCC). Methods This retrospective study was conducted at Liaquat National Hospital, Karachi, Pakistan. A total of 306 biopsy-proven cases of HNSCC were included in the study. Clinical data, which included age, sex, and site of the lesion, were obtained from the clinical referral forms. Resections of the lesions were performed, and the specimens collected were sent to the laboratory for histological evaluation. The histological subtype, perineural invasion (PNI), depth of invasion (DOI), nodal metastasis, and extranodal extension were assessed, and the association of clinicopathological parameters with nodal metastasis was sought.  Results The mean age at diagnosis was 50.26 ± 12.86 years with a female predominance (55.27%), and the mean tumor size was 3.37 ± 1.75 cm. The mean DOI was 1.08 ± 0.67 cm. The most common site of tumor was found to be the oral cavity (68.6%), followed by the tongue (24.2%). Keratinizing SCC (59.5%) was found to be the most prevalent histological subtype. At the time of diagnosis, the majority of the tumors were grade 2 (62.4%). PNI was present in 12.1% of the cases. Nodal metastasis was present in 44.8%, and extranodal extension was present in 17% of the cases. A significant association of nodal metastasis was noted with age, gender, tumor site, tumor size, and DOI. Male patients with HNSCC showed a higher frequency of nodal metastasis than female patients. Patients between the ages of 31 and 50 years with a tumor size of above 4 cm and a DOI of more than 1 cm had a higher frequency of nodal metastasis. Similarly, tumors arising in the oral cavity and the keratinizing subtype were more likely to possess nodal metastasis. Conclusion We found that HNSCCs were more prevalent among the female population, with the most common site being the oral cavity. Nodal metastasis was significantly associated with the keratinizing subtype of SCC, oral cavity location, male gender, and middle age group. Similarly, the tumor size and DOI were important predictors of nodal metastasis in HNSCC in our study.

Sinovac COVID-19 Side Effects in Hypertensive Patients: An Observational Study From Pakistan.

Background The most important factor in combating the coronavirus disease 2019 (COVID-19) pandemic was the provision of safe and effective vaccines. The acceptance of vaccines is impacted by several variables, including beliefs about the vaccine's safety and adverse effects. Vaccine side effects can vary depending on the type, but they are often moderate, localized, transient, and self-limiting. Therefore, this study aimed to assess the prevalence of side effects experienced after receiving the Sinovac vaccine by participants hypertensive and non-hypertensive participants. Methodology This was a cross-sectional, multicenter study that was performed using non-probability sampling. The study duration was six months from May 1, 2022, to October 31, 2022. The study involved 600 individuals who had either received the first or second dose of the Sinovac vaccine. For categorical data, frequencies and percentages were documented. The chi-square test was applied to determine the association between local and systemic side effects among hypertensive and non-hypertensive participants. Results The study findings showed that out of 600 participants, there were 187 (62.3%) males and 113 (37.7%) females with hypertension, and 222 (74.0%) males and 78 (26.0%) females without hypertension, with a significant association (p = 0.002). Following the first dose of the Sinovac vaccine, fever was the most commonly reported side effect in 153 (51.0%) hypertensive participants and 62 (20.7%) non-hypertensive participants, with a significant association (p < 0.001). Similarly, following the second dose of the Sinovac vaccine, fever was the most commonly reported side effect in 108 (36.0%) hypertensive participants and 57 (19.0%) non-hypertensive participants, with a significant association (p < 0.001). Conclusions This study concluded that the presence of hypertension significantly increased the manifestations of local and systemic side effects compared with non-hypertensive participants. Moreover, fever, pain, and swelling at the injection site were the most commonly reported side effects after receiving the first and second doses of the Sinovac vaccine.

Common Side Effects of Pfizer COVID-19 Vaccine: An Experience From Pakistan.

Introduction The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) epidemic spread quickly. Vaccines are now being distributed to stop the infectious spread and halt fatalities. The Pfizer-BioNTech vaccine was the first mRNA-based vaccine introduced to boost immunity against COVID-19; however, it could lead to various adverse reactions. Therefore, the aim of this study was to assess the prevalence of Pfizer vaccine side effects among participants. Methods This was a multicenter cross-sectional study that was performed using a non-probability sampling method. The study period was about six months from March 1, 2022, to August 31, 2022. A total of 1000 participants who received two doses of the Pfizer vaccine met the inclusion criteria. Demographic details of participants, for example, gender, age, comorbidities, Pfizer vaccine with both doses along with booster dose, previous exposure to coronavirus disease 2019 (COVID-19) infection, and the incidence of any local and systemic side effects following the first and second doses of vaccine, were reported.  Results The study findings showed that out of 1000 participants, 644 (64.4%) were males and 356 (35.6%) were females; their mean age was 43.06±14.98 years. Among them, 280 (28.0%) had hypertension and 356 (35.6%) had diabetes. Following the first dose of the Pfizer vaccine, burning at the injection site and fever were the most commonly reported side effects in 704 (70.4%) and 700 (70.0%) participants, respectively. Following the second dose of the Pfizer vaccine, muscle pain was the most commonly reported side effect in 628 (62.8%) participants. Conclusion This study concluded that the most frequent adverse effects of the Pfizer vaccine were burning at the injection site, fever, pain at the injection site, muscle pain, swelling at the injection site, and joint pain. Moreover, the first dose was associated with more side effects than the second dose.