Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: A scoping review.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the accumulation of transthyretin (TTR) protein in the myocardium. The aim of this scoping review is to provide a descriptive summary of the clinical trials and observational studies that evaluated the clinical efficacy and safety of various agents used in ATTR-CM, with a goal of identifying the contemporary gaps in literature and to reveal future research opportunities. METHODS AND RESULTS: The search was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search using several databases for observational and clinical trials investigating the treatment modalities for ATTR-CM was undertaken. We extracted data including study characteristics, primary endpoints, and adverse events from each study. A total of 19 studies were included in our scoping review. 8 were clinical trials and 11 were observational analyses. The drugs evaluated included tafamadis, acoramidis, revusiran, TUDCA and doxycycline, diflusinil, inotersan, eplontersen, and patisiran. Tafamidis has shown to be efficacious in the management of ATTR-CM, particularly when initiated at earlier stages. RNA interference and antisense oligonucleotide drugs have shown promising impacts on quality of life. Additionally, this review identified gaps in the literature, particularly among long-term outcomes, comparative effectiveness, and the translation of research into economic contexts. CONCLUSIONS: Multiple pharmacological options are potential disease-modifying therapies for ATTR-CM. However, many gaps exist in the understanding of these various drug therapies, warranting further research. The future directions for management of ATTR-CM are promising in regard to improving prognostic implications.

Ovarian angiosarcoma: A systematic review of literature and survival analysis.

Ovarian angiosarcoma (OA) is rare, with only sporadic cases reported in English literature. We performed a systematic review of cases published in the PubMed, Science Direct, and Google Scholar databases with the aim of describing the reported clinicopathological features of OA. Fifty-three articles that reported 60 patients were reviewed. Of the 60 patients, 7 (11.6 %) were diagnosed with secondary (metastatic) ovarian angiosarcoma and 53 (88.3 %) were diagnosed with primary ovarian angiosarcoma. The mean age at presentation for ovarian angiosarcoma was 38.3±17.8 years. The average tumor size for ovarian angiosarcoma was 11.9±6.1 cm. Abdominal distention was reported in 45/60 (75 %). Microscopic examination revealed necrosis in 28/60 (46.7 %), pleomorphism in 32/59 (54.2 %), mitotic figures in 44/60 (73.3 %), spindle-shaped cells in 27/36 (75 %), epithelioid-shaped cells in 20/36 (55.5 %), and mixed epithelioid and spindle-shaped cells in 12/36 (33.3 %) patients. On immunohistochemistry CD 31 was positive in 41/41 (100 %), CD 34 in 38/39 (97.4 %), and Factor VIII related antigen in 18/21 (85.7 %) patients. Metastasis was present in 43/60 (71.6 %) patients. Chemotherapy and surgery was performed in 36/52 (69.2 %). The median follow-up time for ovarian angiosarcoma was 7 months (IQR1-IQR3:2-13.5 months). 24 (48 %) of the 50 patients with available survival data were alive and 26/50 (52 %) were dead of disease. Survival analyses (KM curves) revealed that the presence of necrosis (log-rank test; p = 0.05) and absence of spindle-shaped cells (log rank test; p = 0.04) on histopathology were associated with worse outcomes, while treatment with combined chemotherapy and surgical excision was associated with better survival (P < 0.001) therefore, prompt diagnosis and early treatment with combined chemotherapy and surgical excision can prolong survival in OA.

Pitfalls in Urinary Tract Cytopathology.

Urine cytopathology is a cost-effective method to diagnose and follow patients with high grade urothelial carcinoma (HGUC). However, some benign, reactive and metaplastic changes may mimic HGUC and pose a diagnostic challenge for cytopathologists. Summary: Our comprehensive review focuses on summarizing common pitfalls encountered in urine cytopathology, based largely on the experience of the senior author (AC) utilising the diagnostic criteria described in the 2nd edition of The Paris system (TPS) for reporting urinary tract cytopathology and in recent published literature. These include urothelial tissue fragments, instrumented samples, degenerative changes, treatment effects, viral cytopathic changes, iatrogenic and metaplastic changes. Our aim is to provide a clear understanding of these challenges to assist cytopathologists in making accurate diagnoses. Key Message: It's crucial for cytopathologists to recognize benign, reactive and metaplastic lesions that could resemble HGUC. Awareness of these cytological features is essential to minimise diagnostic errors.

Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.

In May 2019, the U.S. Food and Drug Administration approved tafamidis as the first conservative management of transthyretin amyloid cardiomyopathy (ATTR-CM). Our aim in conducting this systematic review and meta-analysis was to assess the efficacy of tafamidis on patients with ATTR-CM. For that purpose, we thoroughly searched PubMed, ScienceDirect, and Clinical trails.gov by using the appropriate search strategy and following predefined inclusion and exclusion criteria, which retrieved 235 articles initially. Of which two randomized controlled trials (RCTs) and one observational study matched our inclusion criteria. A total of 876 patients are included in this analysis. Based on results, tafamidis significantly reduced cardiovascular (CV) mortality in the ATTR-ACT trial and Ochi et al. (OR 0.58; 95% CI: [0.41-0.83], P=0.003, I 2=87%). A subgroup analysis was conducted for CV mortality due to heart failure (OR 0.89; 95% CI: [0.63-1.25], P=0.50, I 2=93%). The results exhibit that tafamidis reduced all causes of mortality (OR 0.45; 95% CI: [0.32-0.64], P≤0.00001, I 2=22%). Furthermore, mortality remained statistically insignificant in patients with heart transplants (OR 1.18; 95% CI: [0.52-2.70], P=0.70, I 2=0%) and patients with cardiac mechanical assist devices (OR 4.15; 95% CI: [0.48-35.66], P=0.20, I 2=0%). This meta-analysis suggests that tafamidis is a safe and efficient drug to use in patients with ATTR-CM and can possess the potential to be a milestone in enhancing the conservative management of the patients.

Angiosarcoma of gallbladder, a literature review.

BACKGROUND: Angiosarcoma of the gallbladder is a rare diagnostic entity rarely encountered by pathologists and has rarely been reported in literature. This review aimed to examine the clinicopathological features, immunohistochemistry, treatment, and outcomes of gallbladder angiosarcoma. METHODS: A search of the PubMed, Science Direct and Google Scholar was done with the search terms ("angiosarcoma" OR "angiosarcomas") AND ("gallbladder" OR "gallbladders"). Based on inclusion and exclusion criteria, only case reports could be used for this review. RESULT: 8 case reports were chosen in the end for analysis. The mean age of the patients at presentation was 65 years. It was most frequently observed in males. Abdominal pain and palpable mass were the most commonly reported symptoms. Cholelithiasis and anemia were also reported. On histopathology morphologically epithelioid appearance of angiosarcoma was evident. Cytokeratin (CK) AE1/AE3, Von willebrand factor, Factor VIII antigen, Vimentin, CD31 were positive. Meanwhile, UEA, CD34, CD117, S-100, Keratin, EMA, and CEA showed negative outcome. Surgery was the preferred method of treatment and a mean 10-months follow-up was done. CONCLUSION: Despite the unavailability of convincing data, histological and immunohistochemical analyses play a major role in the diagnosis of gallbladder angiosarcoma. Nevertheless, more comprehensive clinical studies are required to provide universal guidelines for the treatment and diagnosis of angiosarcoma of the gallbladder.

Primary gallbladder melanoma: A systematic review of literature.

Primary gallbladder melanoma (PGM) is a rare malignancy with only sporadic cases reported in the English literature. We performed a systematic review of the cases published in the PubMed, Science Direct and Google Scholar databases with the aim of describing the reported clinicopathologic features of PGM. Thirty-six articles reporting on 39 patients were reviewed. There was a male predominance, with 23 (64 %) of 36 patients being males. The mean age at presentation was 55 ±16 years. Pain in the right upper quadrant was reported in 20/27 (74 %). The average size of the tumor was 3.5 × 1.9 × 1.4 cm. Gallbladder calculi were reported in 7/27 (26 %). A cholecystectomy was performed in 34/38 (89.5 %). Grossly, the tumor mostly (96.5 %) had polypoid appearances and on microscopic examination, the tumor were predominantly comprised of epithelioid cells 12/17 (70.6 %). Mitotic figures and prominent nucleoli were reportedly found in 8/8 (100 %) and 3/3 (100 %) respectively. Junctional melanocytic components were present in 13/21 (61.9 %). Tumor cells were reportedly immunoreactive for S-100 and HMB-45 in all tested cases. Metastasis were reported in 25/36 (69.4 %), with lymph nodes being the most common site (n = 8), followed by brain (n = 6) and liver (n = 4) for metastasis. At a mean follow-up period of 19 +/- 3 months, 16 (48.5 %) of the 33 patients with available survival data were alive and 17/33 (51.5 %) were dead of disease. There is a lack of unified criteria for the diagnosis of PGM, and future studies should aim to resolve this.

Histiocytic sarcoma in renal transplant patients: a literature review.

BACKGROUND: Histiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed. METHODS: In our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included. RESULT: Based on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality. CONCLUSION: Despite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.

Membranous fat necrosis of gall bladder, a case report and literature review.

INTRODUCTION AND IMPORTANCE: Membranous fat necrosis is a rare histological finding. Despite its low incidence and lack of clinical significance, it can involve various organs. Majority of membranous fat necrosis cases are diagnosed in breast lumps and skin in comparison to intra-abdominal lesions. There has been only one reported case of membranous fat necrosis of gall bladder in literature. CASE PRESENTATION: A 56-year-old female patient with previous history of diabetes mellitus and hypertension was administered due to abdominal pain and fever. Based on her physical exam, lab data, and ultrasonography, she was diagnosed by cholangitis. After primary care, she went under cholecystectomy. The histological finding of gall bladder revealed crenulated fatty membranes phagocytized by macrophages in Hematoxylin and Eosin (H&E) staining. Moreover, necrosis and giant cells were seen on Sudan black staining. Hence, the diagnosis of membranous fat necrosis in gall bladder was made. CLINICAL DISCUSSION: Membranous fat necrosis occurs when peripheral blood circulation is compromised. Ischemia of fat tissue cause fatty membranous material accumulation acting as foreign bodies. Hence, it can attract inflammatory response. Regarding pathology, phagocyted membranous by macrophages and giant cells is diagnostic. Sudan black, Luxol fast blue (LFB), long Ziehl-Neelsen, and D-PAS are positive in membranous fat necrosis. CONCLUSION: Membranous fat necrosis of gall bladder is a rare entity. This is the second reported case of such diagnosis. Nonetheless, further pathological investigations are necessary.

A Challenging Diagnosis Of Rare Co-Existent Multiple Myeloma And Prostate Adenocarcinoma: A Systematic Review Of Case Reports.

Objective: To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma. METHODS: The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters. RESULTS: Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia. Conclusion: Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen. PROSPERO Registration Number: CRD42022334906.

Splenogonadal fusion: A rare case report and literature review.

INTRODUCTION AND IMPORTANCE: Splenogonadal fusion is a rare congenital anomaly occurs when splenic tissue presents near or within a gonad. It mostly involves male children. Although it is benign and rare, making a pre-operation precise diagnosis is challenging which can lead to unnecessary invasive treatments. CASE PRESENTATION: A 3-year-old boy was presented by the chief complaint of a painless mass on the left testis and left inguinal hernia. He had a previous history of bilateral cryptorchidism and orchiopexy. Ultrasonography showed a small mass on the inferior pole of left testis and left reducible inguinal hernia. He went under left orchiectomy and hernia repair. Pathological investigation of the specimen resembled normal splenic tissue next to testicular tissue and the diagnosis of splenogonadal fusion was made. CLINICAL DISCUSSION: Splenogodal fusion cases can be challenging. Pain and sensation of mass in the scrotal sac are the most common presentation of splenogonadal fusion. Testicular malignancies can be considered as their main differential diagnosis, despite the fact that imaging and intra-operation frozen section can be helpful in making a definite diagnosis in some cases. It is mostly diagnosed incidentally during other procedures such as hernia repair or orchiopexy. Since it is benign, removal of tumor without orchiectomy is curative. CONCLUSION: In dealing with testicular mass in children, raising awareness of splenogonadal fusion have utmost importance to prevent unnecessary radical surgical interventions.

The Synergistic Effect of Polystyrene/Modified Boron Nitride Composites for Enhanced Mechanical, Thermal and Conductive Properties.

Thermal conductivity (TC) and thermal stability are the basic requirements and highly desirable properties in thermal management, heat storage and heat transfer applications. This work is regarding the fabrication of polystyrene/boron nitride composites and melt extruded to produce good thermal stability, increased thermal conductivity and enhanced mechanical properties. Our strategy is potentially applicable to produce thermally conductive composites of low cost over large scale. Boron nitride powder is bath sonicated in 10% NH3 solution to avoid its agglomeration and tendency toward entanglement in a polymer matrix. An approximately 67.43% increase in thermal conductivity and 69.37% increase in tensile strength as well as 56 multiple increases in thermal stability of the optimum samples were achieved. The developed polymeric composites are potentially applicable in the electronic industry, especially in electronic devices used for 5G, heat sink and several other aviation applications.

Polystyrene-Sepiolite Clay Nanocomposites with Enhanced Mechanical and Thermal Properties.

Polystyrene (PS)/sepiolite clay nanocomposites were prepared via the melt extrusion technique using vinyl tri-ethoxy silane (VTES) as the compatibilizer and cross-linking agent. Mechanical, thermal, and flame-retardant properties of the newly developed polystyrene-based nanocomposites were determined. Surface morphology was investigated using scanning electron microscopy (SEM), examining the distribution of the filler in various compositions of fabricated composites. Structural analysis of the samples was carried out using the Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) techniques. Thermal stability was determined by thermal gravimetric analysis (TGA), showing a maximum 30.2 wt.% increase in residue by adding sepiolite clay. The results obtained from the dynamic mechanical analyzer (DMA) in terms of the storage modulus, loss modulus and damping factor exhibited better stress transfer rate and effective interfacial adhesion between the filler and the matrix. The higher filler loaded sample showed greater flame retardancy by decreasing the burning rate up to 48%.

Pneumothorax as a Complication of Bevacizumab-Containing Chemotherapy: A Systematic Review of Case Reports.

Bevacizumab is a monoclonal anti-vascular endothelial growth factor (VEGF) antibody that binds to and makes all of the VEGF isoforms inactive, and thus prevents angiogenesis, development, and the spread of the tumor. The most reported side effects after administering bevacizumab include bleeding, high blood pressure, heart failure, proteinuria, thrombosis, and gastrointestinal perforation. Pneumothorax has rarely been reported as a complication of bevacizumab, but with an unclear mechanism. This article aims to explore the occurrence of pneumothorax as a side effect after using bevacizumab through a systematic review of current case reports published on the topic. A literature search was conducted using PubMed, Google Scholar, ScienceDirect, and Directory of Open Access through the utilization of appropriate keywords, and case reports were selected based on predefined inclusion and exclusion criteria. Our results encompass five case reports that were further evaluated for demographic, clinical, and treatment parameters. This systematic review concludes that pneumothorax can occur after bevacizumab-containing chemotherapy although this side effect is relatively rare. Awareness regarding this possible side effect can assist clinicians during their practice in considering pneumothorax as a possible differential diagnosis when encountering patients presenting with pulmonary symptoms after starting bevacizumab-containing chemotherapy; hence, timely diagnosis and treatment can save a life.

Invasive Lobular Carcinoma in Premenopausal Woman: A Delayed Diagnosis Due to Socio-Cultural Factors Prevalent in Pakistan.

A 41-year-old premenopausal woman presented to the outpatient department with a diagnosis of invasive lobular carcinoma. She noticed a lump a year back but did not seek medical attention due to many socio-cultural factors prevalent in Pakistan that prevent her from seeking medical attention earlier. She came in for a check-up after increasing in size of the lump. The bilateral mammogram showed large areas of asymmetrical density in the left upper quadrant. It was followed by an ultrasound-guided biopsy which confirmed the diagnosis of invasive lobular carcinoma. Due to stage 3, it was recommended to have CT and an MRI of the breast to assess the extent of the disease. Tissue immunohistochemistry was also requested, which came back as ER-positive, PR-positive, and HER2/neu negative. MRI of the breast revealed a 4.2 x 3.3cm heterogeneously enhancing asymmetric mass-like enhancement area within the left breast outer quadrant with an adjacent spiculated nodular lesion measuring 2.2 cm. CT chest/abdomen/pelvis with contrast showed left breast with minimal parenchymal asymmetry and a small 9 mm node seen in the left axilla. There was no evidence of metastasis. The patient was started on neoadjuvant therapy to minimize systemic disease, followed by mastectomy. This case highlights socio-cultural factors prevalent in Pakistan that lead to delays in the diagnosis and treatment of invasive lobular carcinoma. The outcome had been better if the patient sought medical attention sooner at an earlier stage. We also propose strategies to raise awareness in Pakistan for the timely diagnosis and treatment of breast cancer.

Synthesis of Magnetic Fe3O4 Nano Hollow Spheres for Industrial TNT Wastewater Treatment.

The aim of the present work was to synthesize magnetite (Fe3O4) nano hollow spheres (NHS) via simple, one-pot, template-free, hydrothermal method. The structural, morphological, and surface analysis of Fe3O4 NHS were studied by scanning electron microscopy (SEM), x-ray diffraction technique (XRD), Fourier transform infrared spectroscopy FTIR and burner-Emmett-teller (BET). The as obtained magnetic (Fe3O4) NHS were used as an adsorbent for treating industrial trinitrotoluene (TNT) wastewater to reduce its Chemical Oxygen Demand (COD) values. Adsorption capacity (Qe) of the NHS obtained is 70 mg/g, confirming the attractive forces present between adsorbent (Fe3O4 NHS) and adsorbate (TNT wastewater). COD value of TNT wastewater was reduced to >92% in 2 h at room temperature. The adsorption capacity of Fe3O4 NHS was observed as a function of time, initial concentration, pH, and temperature. The applied Fe3O4 NHS was recovered for reuse by simply manipulating its magnetic properties with slight shift in pH of the solution. A modest decrease in Qe (5.0−15.1%) was observed after each cycle. The novel Fe3O4 NHS could be an excellent candidate for treating wastewater generated by the intermediate processes during cyclonite, cyclotetramethylene-tetranitramine (HMX), nitroglycerin (NG) production and other various environmental pollutants/species.

Histiocytic Sarcoma Secondary to Gastrointestinal Stromal Tumors: A Literature Review.

Histiocytic sarcoma (HS) is a rare tumor that may result from the transdifferentiation of preexisting hematolymphoid neoplasms in a subset of patients. There are instances of correlation or concurrence between HS and a number of cancers, particularly B-cell-associated hematopoietic tumors. Only three cases of HS occurring subsequent to or concurrently with gastrointestinal stromal tumors (GIST) have been recorded. Our main objective was to give an overview of demographics, clinical signs and symptoms, histopathological findings, and immunohistochemical and molecular analysis when HS develops secondary to or concurrently with GIST. A search of PubMed, Google Scholar, and ScienceDirect was undertaken using Medical Subject Headings (MeSH) keywords. According to the findings of our review, there were two males (66.6%) and one female (33.3%). The average age of patients at presentation was 59.6 years. On the immunohistochemistry, three patients were positive for cluster of differentiation (CD) 68 (100%), two patients were positive for CD 163 (67%), one patient was positive for leukocyte common antigen (LCA) (33%), and only one patient was positive for CD 4, CD 10, CD 31, CD 45, human leukocyte antigen (HLA)-DR, lysozyme, and vimentin (33%). On molecular investigation, the gastric mass of only one patient (33.33%) contained a KIT mutation on exon 11. Emperipolesis was observed in one patient (33.33%) on histological examination. Our study provides an important overview of the available literature and gives insight into important diagnostic markers of HS when it occurs secondary to or concurrently with GIST.

Measurement of radioactivity in the soil of Bahawalpur division, Pakistan.

Bahawalpur is the largest division of the Punjab province in Pakistan. It is larger than many countries of the world. Gamma activity from the naturally occurring radionuclides namely 226Ra, 232Th, the primordial radionuclide 40K and the artificial radionuclide 137Cs was measured in the soil of the Bahawalpur division using gamma spectrometry technique. The mean activity of 226Ra, 232Th, 40K and 137Cs were found to be 32.9 +/- 0.9, 53.6 +/- 1.4, 647.4 +/- 14.1 and 1.5 +/- 0.2 Bq kg(-1), respectively. The mean radium equivalent activity Raeq, external hazard index, internal hazard index and terrestrial absorbed dose rate for the area under study are 158.5 +/- 4.1 Bq kg(-1), 0.4, 0.5 and 77.32 nGy h(-1), respectively. The annual effective dose equivalent to the public was found to be 0.5 mSv.