Significance of Estrogen/Progesterone Receptor Expression in Metaplastic Breast Carcinoma.

Introduction: Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. Methods: This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes' archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. Results: The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. Conclusion: MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis.

Diagnostic accuracy of intraoperative frozen section for margin evaluation of oral cavity squamous cell carcinoma.

OBJECTIVES: Intraoperative frozen-section evaluation is a valuable technique for detecting positive margins intraoperatively for oral squamous cell carcinoma. We conducted this study to determine the diagnostic accuracy of frozen section in detecting margin status and the effect of tumor grade and stage on diagnostic accuracy. RESULTS: A total of 251 biopsy-proven cases of oral squamous cell carcinoma were included in this study. The tissue specimen resected during surgery was sent to the laboratory for frozen section evaluation. The frozen section results were then compared with the permanent section results to determine the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. The mean age of the patients included in the study was 51.65 ± 10.03 years, with male predominance (55.4%). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of frozen section were 88.81%, 94.84%, 95.20%, 88.10%, and 91.63%, respectively. We conclude that frozen section is a useful technique in determining the margin status intraoperatively in oral cancers, with high diagnostic accuracy. Moreover, certain clinical parameters such as age, gender, disease duration, and tumor stage and grade appear to affect the diagnostic accuracy of frozen section.

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.

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.

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.

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 Profile of a Cohort of Patients With Malignant Melanoma in the United Kingdom.

Introduction Malignant melanoma (MM) is potentially a fatal type of skin cancer and a major health concern for the Caucasian population. It is a heterogeneous disease with a wide spectrum of manifestations. Therefore, in this study, we evaluated the clinicopathological characteristics of MM. Methods We retrospectively studied the clinicopathological characteristics of MM in 167 biopsy-proven cases of MM reported between January 2020 and December 2021 at Kings Mill Hospital, Sutton-in-Ashfield, United Kingdom. Clinical data such as the age, sex, and anatomical site of the lesion were obtained from the clinical referral forms. Biopsies of the lesions were performed, and the specimens collected were sent to the laboratory for histopathological study and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation evaluation. Formalin-fixed paraffin-embedded blocks (FFPE) were prepared, sectioned, and stained with hematoxylin and eosin for histological examination. Results A total of 167 cases of MM were included in the study. The age range was 23-96 years, with the median age at diagnosis found to be 66 years; males were more commonly affected (52.1%). The median Breslow thickness was 1.20 mm. The median mitotic activity was 1.0/mm2. The lower limb was the most common site of involvement (27.5%), followed by the thorax (25.1%). The most common histological subtype was superficial spreading melanoma (SSM) (77.8%), followed by nodular melanoma (14.4%). The in situ component was present in 95.8% of cases; a majority (92.2%) of the cases showed vertical growth phase, 71.9% of cases were at Clark's level IV of invasion, regression was noted in 70.7% of cases, ulceration was present in 21.6% of cases, and microsatellites were present in 3% of cases. Perineural invasion was present in 3% of cases, and lymphovascular invasion (LVI) was present in 4.2% of cases. BRAF mutation testing was performed on 36 cases, out of which 20 cases (55.6%) showed BRAF mutation. Acral lentiginous melanoma and nodular melanoma were most likely to show ulceration (66.7% and 37.5%, respectively). SSM and lentigo maligna melanoma were more likely to be associated with regression. Conclusion The study demonstrated that MM is prevalent among the elderly population with male predominance; SSM was found to be the most common subtype. The study further demonstrated various clinicopathological features of MM and its association with histological subtypes.

Direct oral anticoagulants vs. vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.

Optimal treatment regimen for patients with antiphospholipid syndrome (APS) remain unclear. Therefore, the authors sought to compare the outcomes of vitamin K antagonists (VKAs) vs. direct oral anticoagulants (DOACs) in patients with APS. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials comparing efficacy and safety of VKAs and DOACs inhibitors in patients with APS. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. Results: The analysis included 625 patients from four randomized controlled trials and one post hoc analysis. Meta-analysis showed statistically non-significant difference between DOACs inhibitors and VKAs in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P=0.11, I2=50%]. Consistent results were revealed among patients with the previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P=0.75, I2=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P=0.31, I2=15%] and patients who were triple antiphospholipid positive [RR 4.12 (95% CI 0.46, 37.10); P=0.21, I2=58%]. DOACs inhibitors were significantly associated with increased risk of stroke [RR 8.51 (95% CI 2.35, 3.82); P=0.47, I2=0%]. Conclusion: DOACs exhibited increased risk of stroke among patients with APS. In addition, although not significant, the higher RRs among patients on DOACs may indicate higher risk of thrombotic events associated with DOACs.

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.

Machine Learning-Based Predictive Model for Tensile and Flexural Strength of 3D-Printed Concrete.

The additive manufacturing of concrete, also known as 3D-printed concrete, is produced layer by layer using a 3D printer. The three-dimensional printing of concrete offers several benefits compared to conventional concrete construction, such as reduced labor costs and wastage of materials. It can also be used to build complex structures with high precision and accuracy. However, optimizing the mix design of 3D-printed concrete is challenging, involving numerous factors and extensive hit-and-trail experimentation. This study addresses this issue by developing predictive models, such as the Gaussian Process Regression model, Decision Tree Regression model, Support Vector Machine model, and XGBoost Regression models. The input parameters were water (Kg/m3), cement (Kg/m3), silica fume (Kg/m3), fly ash (Kg/m3), coarse aggregate (Kg/m3 & mm for diameter), fine aggregate (Kg/m3 & mm for diameter), viscosity modifying agent (Kg/m3), fibers (Kg/m3), fiber properties (mm for diameter and MPa for strength), print speed (mm/sec), and nozzle area (mm2), while target properties were the flexural and tensile strength of concrete (MPa data from 25 literature studies were collected. The water/binder ratio used in the dataset ranged from 0.27 to 0.67. Different types of sands and fibers have been used, with fibers having a maximum length of 23 mm. Based upon the Coefficient of Determination (R2), Root Mean Square Error (RMSE), Mean Square Error (MSE), and Mean Absolute Error (MAE) for casted and printed concrete, the SVM model performed better than other models. All models' cast and printed flexural strength values were also correlated. The model's performance has also been checked on six different mix proportions from the dataset to show its accuracy. It is worth noting that the lack of ML-based predictive models for the flexural and tensile properties of 3D-printed concrete in the literature makes this study a novel innovation in the field. This model could reduce the computational and experimental effort required to formulate the mixed design of printed concrete.

Clinicopathological Parameters Associated With Peritoneal Involvement in Epithelial Ovarian Tumors.

Introduction Ovarian tumors remain one of the leading malignancies of the female genital tract, with a high mortality rate due to their insidious onset and lack of detection at an earlier stage. These tumors metastasize by direct extension into the neighboring pelvic organs; hence, the detection of peritoneal metastasis is valuable for staging and prognostic purposes. Peritoneal wash cytological analysis is an effective predictor of the involvement of the ovarian surface and peritoneal dissemination even in subclinical involvement of the peritoneum. The study aims to determine the significance of peritoneal wash cytology as a prognostic parameter and correlate it with various clinicohistological features. Methods A retrospective study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan, between July 2017 and June 2022. During this period, all the cases of ovarian tumors (borderline and malignant) that underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omental and lymph node sampling were included in the study. After opening the abdominal cavity, the free fluid present was aspirated immediately, the peritoneum was lavaged with 50-100 mL of warm saline, and samples were collected and sent for cytological analysis. Four cytospin smear slides and cell block preparation were prepared. The findings of peritoneal cytology were correlated with various clinicohistological features. Results A total of 118 cases of ovarian tumors were included in the study. Serous carcinoma was the most common sub-type (50.8%), followed by endometrioid carcinoma (14.4%), and the mean age at diagnosis was found to be 49.9±14.9 years. The mean tumor size was 11.2 cm. The majority of the cases of ovarian carcinoma were of high grade (78.8%), with capsular invasion present in 61% of cases. Positive peritoneal cytology was noted in 58.5% of cases, with omental involvement in 52.5% of cases. Serous carcinoma showed the highest frequency of positive cytology (69.6%) and omental metastasis (74.2%). Apart from tumor type, positive peritoneal cytology showed a significantly positive correlation with age, tumor grade, and capsular invasion. Conclusion Based on our study findings, we conclude that peritoneal wash cytology is a sensitive indicator of the peritoneal spread of ovarian carcinoma, with a significant prognostic value. Serous carcinomas, especially high-grade with capsular invasion, were found to be predictors of peritoneal involvement of ovarian tumors. Although we found smaller tumors to be associated with peritoneal disease more compared to larger ones, this most likely is attributed to tumor histology, as larger tumors were most commonly mucinous compared to serous carcinomas.

Effectiveness of non-invasive respiratory support strategies in patients with COVID-19: A systematic review and meta analysis.

Background: BackgroundThe effectiveness of non-invasive respiratory strategies, namely CPAP and HFNO, in reducing the risk of mortality and tracheal intubation in patients with severe COVID-19 is not well established. Methods: A thorough literature search was conducted across 3 electronic databases (Medline, EMBASE and Cochrane Central) from inception through July 2022. Randomized controlled trials (RCTs) and observational studies assessing the impact of CPAP or HFNO on clinical outcomes in patients infected with COVID-19 were considered for inclusion. End-points included all-cause mortality and risk of tracheal intubation. Evaluations were reported as risk ratios (RRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. I2 index was used to assess heterogeneity. Results: From the 1041 articles retrieved from initial search, 7 potentially relevant studies (n = 2831 patients) were included in the final analysis. Compared to conventional oxygen therapy, non-invasive respiratory strategies reduced the risk of tracheal intubation (RR = 0.84, [95% CI 0.72, 0.98]; p = 0.02, I2 = 43%) and all-cause mortality (RR = 0.83, [95% CI 0.71-0.97]; p = 0.02, I2 = 0%) in patients infected with COVID-19 However, reduction in length of hospital stay was not significant between the non-invasive respiratory group and conventional oxygen therapy (MD = -0.60, [95% CI -2.17 - 0.98]; p = 0.46, I2 = 26%). Conclusion: This meta-analysis supports the application of non-invasive respiratory strategy is feasible as it can delay the start of tracheal intubation and reduce mortality rates among patients infected with COVID-19.

Aggressive Angiomyxoma, Angiomyofibroblastoma, and Cellular Angiofibroma of the Lower Female Genital Tract: Related Entities With Different Outcomes.

Introduction Mesenchymal tumors of the lower female genital tract (FGT) are a miscellaneous group of tumors that include aggressive angiomyxoma (AAM), angiomyofibroblastoma (AMFB), cellular angiofibroma (CAF), and related entities. Histologically, these tumors are composed of stromal cells admixed with vessels, with some minor histological differences. An accurate diagnosis of these tumors is important owing to the differences in the outcome. In this study, we determined the clinicopathological characteristics of these tumors in our population and their association with recurrence.  Methods This was a retrospective cross-sectional study conducted at the Department of Histopathology, Aga Khan University, from January 2005 to December 2019 over a period of 15 years. A total of 207 cases that were diagnosed as AAM, AMF, and CAF were selected for inclusion in the study. Clinical data, including age and location of the lesion, were obtained from histopathology referral forms. Tissue blocks of all cases were retrieved. Follow-up data were obtained from the patient files, and information regarding disease recurrence was recorded. One histological section from each tissue block was stained with hematoxylin and eosin stain, and histopathological findings were recorded. Additionally, immunohistochemical (IHC) studies, including vimentin, smooth muscle actin (SMA), and desmin were conducted on representative tissue blocks. Final histopathological diagnoses were rendered considering clinical, histopathological, and IHC findings. Results The median age of patients involved in the study was 33 years and the median tumor size was 5 cm with a predilection for the vulva (47.3%). AAM showed a predilection for patients between the ages of 31-45 years, while AMFBs and CAFs were most common in younger age groups of less than 30 years. In 46.8% of cases, the tumor size of AAM was between 6 and 10 cm, while in all cases of CAF (100%) and the majority of AMFB cases (53.2%) the tumor size was smaller than 5 cm. Histologically, in all cases of AAM, the lesional cells were spindle (100%), whereas, in 13% of cases epitheloid cells were observed, with myxoid stroma in 92.2% cases. The presence of stromal smooth muscle was noted in 42.9% of cases, in 79.2% of cases the vessels were thick-walled, with 54.5% having hyalinized vessels, and most of the cases (77.9%) had ill-defined borders. Among IHC findings, AMFB was most frequently positive for actin (62.2%), while AAM and AMFB showed more frequent staining for desmin compared to CAF. A significantly higher recurrence rate was observed in AAM (27.3%), compared to AMFB and CAF. A significant association of recurrence was seen with tumor size. It was noted that the recurrence rate was directly proportional to the size of the tumor and was highest (60%) with a tumor size of more than 10 cm. Conclusion In our study, we noted that AMFB was the most common among the three mesenchymal tumors of the lower FGT. In contrast, AAM had the highest recurrence rate, and recurrence was significantly associated with tumor size. Histological findings, especially the type of stromal cells and background vasculature, are of utmost importance for the correct recognition of these tumors, while the role of IHC studies is limited.

Clinicopathological Features of Alopecia With an Emphasis on Etiology and Histopathological Characteristics of Scarring Alopecia.

Introduction Alopecia is a common dermatological condition with varied etiologies based on age, gender and geographic location. Non-cicatricial (non-scarring) alopecia is more common but often not biopsied. Alternatively, primary cicatricial (scarring) alopecia is diagnostically more challenging and more commonly biopsied to determine the etiology. In this study, we evaluated the clinicopathological characteristics of alopecia in our population. Methods We conducted a retrospective study at the Department of Histopathology, Liaquat National Hospital and Medical College, Pakistan. A total of 104 patients were enrolled in the study who underwent scalp biopsy for alopecia over a period of 11 years. Clinical data were obtained from clinical referral forms, which included age, sex of the patients and duration of the lesions. Three hematoxylin and eosin-stained tissue sections, along with periodic acid-Schiff (PAS), PAS with diastase and collagen stains were examined, and histopathological diagnosis was rendered. Results Our study demonstrated that alopecia was more prevalent among females, accounting for 73.1% of cases. Most of the patients belonged to the age group of <35 years (53.8%). The type of alopecia in 88.5% of the cases was scarring, while there were 11.5% cases of non-scarring alopecia. The most common diagnoses were discoid lupus erythematosus (DLE) (23.1%) and pseudopelade of Brocq (PB) (23.1%), followed by lichen planopilaris (LPP) (15.4%). A significant association was noted between the histological features and the diagnosis, as epidermal atrophy was the most common histological feature in most cases of DLE, followed by periadnexal infiltrates, lymphocytic infiltrates, follicular plugging and basement membrane thickening. In LPP, the most common histological features were perifollicular infiltrates and fibrosis. In PB, the frequently recurring histological features in most cases were the loss of sebaceous glands, dermal fibrosis and epidermal thinning. Conclusion In this study, we demonstrated the key role of skin punch biopsy and histology in determining the accurate etiology of scarring alopecia. We found discoid lupus erythematosus and pseudopelade of Brocq to be the most common causes of scarring alopecia, followed by lichen planopilaris.

Impact of Histological Type and Grade on the Diagnostic Accuracy of Intraoperative Frozen Section for Detecting Breast Cancer Metastasis to Axillary Sentinel Lymph Nodes.

Introduction Intraoperative sentinel lymph node (SLN) evaluation is the standard of care in patients with clinically node-negative breast cancer. The most common histological subtype of breast carcinoma is invasive ductal carcinoma (IDC), followed by invasive lobular carcinoma (ILC). Alternatively, histological grades vary from grades G1 to G3. Therefore, in this study, we evaluated the diagnostic accuracy of frozen section (FS) for detecting breast cancer metastasis to SLNs with respect to histological subtypes and grades. Methods A retrospective observational study was conducted in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, from January 2013 till December 2020, over a duration of eight years. A total of 540 cases of primary breast cancer, undergoing upfront breast surgery were included in the study. Intraoperatively, SLNs were identified and sent for FS. After FS reporting, the remaining tissue was submitted for final (paraffin) section examination after formalin fixation, and results of FS and final (paraffin) sections were compared. Results The mean age of the patients included in the study was 52.05±12.42 years, and the median number of SLNs was three (ranging from one to 14). The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of intraoperative FS were 88.2%, 100%, 100%, 92.5%, and 95.2%, respectively. The sensitivity of FS for IDC was 88.3%, whereas it was 85.7% for ILC. Alternatively, the sensitivity of FS for grade G1, G2, and G3 tumors was 78.3%, 91.5%, and 90.2%, respectively. The false-negative rate for grade G1 tumors was 21.7%, which was higher than G2 and G3 tumors (8.5% and 9.8%, respectively). Similarly, the false-negative rate for cases where the number of SLNs was more than three was only 5.4%, which was lower than cases with a single and two to three SLNs sent on FS (23.1 and 14.7%, respectively). Conclusion The sensitivity of intraoperative FS for detecting ILC metastasis to axillary SLNs was not substantially different from IDC; however, histological grade affects the sensitivity of FS diagnosis, with lower-grade tumors having low sensitivity. Moreover, increasing the number of SLNs sent intraoperatively on FS improves the sensitivity of FS for detecting breast cancer metastasis to axillary SLNs.

Morphological Spectrum of Vesiculobullous Skin Lesions: An Institutional Perspective.

Introduction A vesiculobullous lesion of the skin encompasses a group of dermatological disorders with protean clinicopathological features. They usually occur as a part of the spectrum of various infectious, inflammatory, drug-induced, genetic, and autoimmune disorders. Therefore, accurate diagnosis of these lesions is essential for appropriate management and to reduce the associated morbidity and mortality. The conventional skin punch biopsy is the mainstay in the diagnosis of dermatological diseases, especially when combined with confirmatory tests, such as direct immunofluorescence (DIF). Our study evaluated the clinicopathological spectrum of vesiculobullous lesions. Methods We studied 150 cases of vesiculobullous lesions at the Department of Histopathology, Liaquat National Hospital and Medical College Karachi, Pakistan. Written and informed consent was taken from the patients followed by skin punch procedure in which three biopsies were obtained, which included one biopsy from the lesion and two peri-lesional biopsies. One peri-lesional biopsy was sent in cryomatrix for DIF studies, whereas the other two were sent in formalin to follow the standard tissue-processing protocol. Results Our results showed that most patients belonged to the geriatric age group of more than 50 years (44.7%), and 54.7% of the patients were females. Total 74.7% of the patients had generalized lesions, followed by lower limbs (9.3%) and trunk (7.3%) involvement. Most patients were diagnosed with bullous pemphigoid (31.3%), followed by pemphigus vulgaris (27.3%), dermatitis herpetiformis (15.3%), Darier's disease (14.7%), pemphigus foliaceus (4.7%), epidermolysis bullosa (2%), linear immunoglobulin A dermatosis (2%), paraneoplastic pemphigus (0.7%), and drug reactions (0.7%). DIF studies were applied on 60 cases, out of which complement protein C3c was the most commonly deposited protein (53.3%). Conclusion Our study emphasized the diagnostic role of skin punch biopsy in the proper evaluation of vesiculobullous skin lesions. Histopathology is the cornerstone diagnostic tool in this regard, with DIF being a useful adjunct.

Optimal Lateral Displacement in Automatic Close-Range Photogrammetry.

Based on the use of automatic photogrammetry, different researchers made evident that the level of overlap between adjacent photographs directly affects the uncertainty of the 3D dense cloud originated by the Structure from Motion/Image Matching (SfM/IM) process. The purpose of this study was to investigate if, in the case of a convergent shooting typical of close-range photogrammetry, an optimal lateral displacement of the camera for minimizing the 3D data uncertainty could be identified. We examined five different test objects made of rock, differing in terms of stone type and visual appearance. First, an accurate reference data set was generated by acquiring each object with an active range device, based on pattern projection (σz = 18 µm). Then, each object was 3D-captured with photogrammetry, using a set of images taken radially, with the camera pointing to the center of the specimen. The camera-object minimum distance was kept at 200 mm during the shooting, and the angular displacement was as small as π/60. We generated several dense clouds by sampling the original redundant sequence at angular displacements (nπ/60, n = 1, 2, … 8). Each 3D cloud was then compared with the reference, implementing an accurate scaling protocol to minimize systematic errors. The residual standard deviation of error made consistently evident a range of angular displacements among images that appear to be optimal for reducing the measurement uncertainty, independent of each specimen shape, material, and texture. Such a result provides guidance about how best to arrange the cameras' geometry for 3D digitization of a stone cultural heritage artifact with several convergent shots. The photogrammetric tool used in the experiments was Agisoft Metashape.

Impact of diastolic dysfunction on long-term mortality and quality of life after transcatheter aortic valve replacement.

BACKGROUND: There is conflicting data as to whether diastolic dysfunction (DD) affects the prognosis of patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: Consecutive patients undergoing TAVR underwent assessment of DD with preoperative echocardiography and NT-pro BNP. Long-term survival was ascertained every 6 months by clinic visits or phone. DD was graded according to the new American Society of Echocardiography recommendations. Health status was assessed at baseline and 30 days post-procedure using the KCCQ-12 questionnaire. Long-term survival was displayed using Kaplan-Meier curves according to NT-pro BNP levels and DD grades. RESULTS: We included 222 patients, mean age 78 (±8) years, median STS score 4 (interquartile range = 3-7), median follow-up time 385 days (IQR = 180-640). DD was absent in 25, Grade I in 13, Grade II in 74, Grade III in 24, and indeterminate in 86 patients. Advanced (Grades II-III) DD was associated with higher pre-procedural NT-pro BNP levels (p < .001), worse quality of life (p < .001) but similar surgical risk (p = .43). Advanced and indeterminate DD were associated with increased long-term mortality (25-28% vs. 5%, p = .02) and elevated NT-pro BNP levels (26.4% vs. 9.8%, p = .05). Improvements in quality of life measures were seen in all DD groups (median change in KCCQ score no or Grade I DD:14 [3-21] vs. Grades II-III DD: 15 [16-26; p = .37]). CONCLUSION: Preoperative NT-pro BNP levels and echocardiographic indices of indeterminate or advanced DD are associated with increased long-term mortality after TAVR but similar improvements in quality of life.

An Observational Study of Elderly Veterans With Initially Asymptomatic Severe Aortic Stenosis.

BACKGROUND: The optimal timing of aortic valve replacement (AVR) among patients with asymptomatic severe aortic stenosis (AS) remains uncertain and controversial. METHODS: We conducted a cohort study of consecutive patients with severe AS (mean gradient, 40 mm Hg; aortic valve area <1 cm², or peak velocity ≥4 m/s) who were asymptomatic at the time of echocardiography (2005-2015). Outcomes included mortality, AVR, or AS symptoms. Kaplan-Meier curves and the log-rank test were used to compare the outcomes of patients treated with AVR compared with conservative management. Cox proportional-hazards regression analysis was performed to identify predictors of long-term mortality. RESULTS: Of 1181 echocardiograms and medical records reviewed, a total of 324 patients met inclusion criteria. The mean age of the study cohort was 78 ± 10 years and 97% were male. The median follow-up time was 8 years (interquartile range [IQR], 7-10 years), during which 147 patients (51%) underwent AVR and 94 patients (29%) died. The median survival for patients treated with AVR was 10 years (IQR, 9-10 years) and for patients managed conservatively was 4.8 years (IQR, 3.7-5.7 years; P<.001). A total of 47 patients (14% of the cohort and 48% of deaths) expired before AS symptoms were documented in their medical records. Independent predictors of mortality were age (hazard ratio [HR] per increase in decile, 1.14; 95% CI, 1.05-1.24; P<.01) and performance of AVR during follow-up (HR, 0.15; 95% CI, 0.9-0.28; P<.01). CONCLUSION: A significant proportion of elderly patients with initially asymptomatic severe AS died before symptoms were identified. Our study highlights the difficulty of relying on symptoms alone for timely referral to AVR surgery.

Cytogenetic Abnormalities in Myelodysplastic Syndromes: An Overview.

Karyotype is one of the main constituents of the International Prognostic Scoring System (IPSS) and revised-IPSS that are the cornerstones for the prognostication of patients with myelodysplastic syndromes (MDS). Del(5q), -7/del(7q), +8 and -Y are among the most extensively studied cytogenetic abnormalities in MDS. The same applies for normal karyotype. There are hundreds of other rare cytogenetic abnormalities that have been reported in MDS, included but not limited to -X, 3q abnormalities, +13/del(13q), i(17q), +21/-21. However, due to a very low number of patients, their impact on the prognosis of MDS is limited. Knowledge of the molecular consequences of different cytogenetic abnormalities allows us to modify treatment regimens based on drugs most active against the specific karyotype present, allowing for the opportunity to individualize MDS treatment and improve patient care and prognosis.