Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra.

Thrombotic microangiopathy (TMA) is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys. This review is specifically focused on post-transplant TMA (PT-TMA) involving kidney transplant recipients. Its reported prevalence in the latter population varies from 0.8% to 14% with adverse impacts on both graft and patient survival. It has many causes and associations, and the list of etiologic agents and associations is growing constantly. The pathogenesis is equally varied and a variety of patho genetic pathways lead to the development of microvascular injury as the final common pathway. PT-TMA is categorized in many ways in order to facilitate its management. Ironically, more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case. Pathologically, the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature. Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists. The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase. Management of the condition is also challenging and still largely empirical. It varies from simple maneuvers, such as plasmapheresis, drug withdrawal or modification, or dose reduction, to lifelong complement blockade, which is very expensive. A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective. This review aims to increase the awareness of relevant stakeholders regarding this important, potentially treatable but under-recognized cause of kidney allograft dysfunction.

Mortality and mode of dialysis: meta-analysis and systematic review.

BACKGROUND: The global use of kidney replacement therapy (KRT) has increased, mirroring the incidence of acute kidney injury and chronic kidney disease. Despite its growing clinical usage, patient outcomes with KRT modalities remain controversial. In this meta-analysis, we sought to compare the mortality outcomes of patients with any kidney disease requiring peritoneal dialysis (PD), hemodialysis (HD), or continuous renal replacement therapy (CRRT). METHODS: The investigation was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Cochrane Library, and Embase databases were screened for randomized trials and observational studies comparing mortality rates with different KRT modalities in patients with acute or chronic kidney failure. A random-effects model was applied to compute the risk ratio (RR) and 95% confidence intervals (95%CI) with CRRT vs. HD, CRRT vs. PD, and HD vs. PD. Heterogeneity was assessed using I2 statistics, and sensitivity using leave-one-out analysis. RESULTS: Fifteen eligible studies were identified, allowing comparisons of mortality risk with different dialytic modalities. The relative risk was non-significant in CRRT vs. PD [RR = 0.95, (95%CI 0.53, 1.73), p = 0.92 from 4 studies] and HD vs. CRRT [RR = 1.10, (95%CI 0.95, 1.27), p = 0.21 from five studies] comparisons. The findings remained unchanged in the leave-one-out sensitivity analysis. Although PD was associated with lower mortality risk than HD [RR = 0.78, (95%CI 0.62, 0.97), p = 0.03], the significance was lost with the exclusion of 4 out of 5 included studies. CONCLUSION: The current evidence indicates that while patients receiving CRRT may have similar mortality risks compared to those receiving HD or PD, PD may be associated with lower mortality risk compared to HD. However, high heterogeneity among the included studies limits the generalizability of our findings. High-quality studies comparing mortality outcomes with different dialytic modalities in CKD are necessary for a more robust safety and efficacy evaluation.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Association of burnout and harassment among cardiology trainees: Pakistan's perspective.

OBJECTIVE: This study explores the relationship between sexual harassment and burnout among cardiology trainees, shedding light on the prevalence and impact of these experiences in medical practice. METHODS: A cross-sectional online survey was conducted among 518 respondents, with 420 responding to the Sexual Experience Questionnaire (SEQ). The survey measured harassment experiences and their impact on burnout, especially among female physicians. Correlations were analyzed to understand the association between these variables. RESULTS: Out of 1,375 invitees, we received 671 (48.8 %) responses. The study population was divided into two main groups: males (359) and females (312). The study identified a high prevalence of sexual harassment experiences among female physicians, with incidents occurring primarily during training. Moderate to large correlations were observed between SEQ subscales related to colleagues and patients and their families. While sexual harassment was not significantly related to burnout, this study suggests the need for interventions to create a safer medical workplace. Approximately 22 % of male participants (n = 359) reported career-related inappropriate sexual incidents, with 28 % of male physicians experiencing weekly burnout. Among female participants (n = 312), around 37 % reported inappropriate incidents, while 42 % of female physicians felt weekly burnout. CONCLUSION: Sexual harassment in medicine is a pervasive issue with potential implications for physician well-being. Initiatives aimed at changing the organizational response and fostering a more equitable environment are warranted to address this critical concern.

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.

Exploring the Cardiovascular Benefits of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: Expanding Horizons Beyond Diabetes Management.

Globally, cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality. The risk of cardiovascular disease is markedly increased in individuals with type 2 diabetes mellitus (T2DM), making managing cardiovascular health a top priority. Initially developed for their glucose-lowering properties, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a transformative class of pharmaceuticals with profound cardiovascular benefits that extend far beyond glycemic control. One of the most striking findings is the substantial reduction in major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality, observed in clinical trials evaluating SGLT2 inhibitors. These extraordinary cardioprotective effects are demonstrated by landmark trials such as EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58, which are discussed in detail. In addition, SGLT2 inhibitors have demonstrated positive outcomes in heart failure (HF) with reduced ejection fraction, which has led to their incorporation into HF treatment guidelines. SGLT2 inhibitors offer renoprotection by delaying the progression of diabetic kidney disease, reducing albuminuria, preserving glomerular filtration rates, and their immediate cardiovascular benefits. We investigate the potential mechanisms underlying these renal benefits, focusing on the role of hemodynamic alterations and intraglomerular pressure reduction. In addition, SGLT2 inhibitors have a distinct diuretic effect that can contribute to volume reduction and symptom alleviation in patients with heart failure (HF). This diuretic action, distinct from conventional diuretics, warrants additional research to optimize their use in T2DM and HF patients. The risk of euglycemic diabetic ketoacidosis, genital mycobacterial infections, and bone fractures are also discussed. Understanding these issues is essential for making educated clinical decisions. In conclusion, SGLT2 inhibitors have transcended their initial function as anti-diabetic agents to become essential components of cardiovascular and renal protection strategies in T2DM patients. Their diverse benefits, which include cardioprotection, renoprotection, and the potential for HF management, highlight their potential to transform cardiovascular medicine. Optimizing the use of SGLT2 inhibitors in clinical practice bears the promise of improved cardiovascular outcomes for patients with T2DM and beyond as we navigate this changing landscape.

Charting the Progress of Epilepsy Classification: Navigating a Shifting Landscape.

Epilepsy, a neurological disorder characterized by recurrent seizures, has witnessed a remarkable transformation in its classification paradigm, driven by advances in clinical understanding, neuroimaging, and molecular genetics. This narrative review navigates the dynamic landscape of epilepsy classification, offering insights into recent developments, challenges, and the promising horizon. Historically, epilepsy classification relied heavily on clinical observations, categorizing seizures based on their phenomenology and presumed etiology. However, the field has profoundly shifted from a symptom-based approach to a more refined, multidimensional system. One pivotal aspect of this evolution is the integration of neuroimaging techniques, particularly magnetic resonance imaging (MRI) and functional imaging modalities. These tools have unveiled the intricate neural networks implicated in epilepsy, facilitating the identification of distinct brain abnormalities and the categorization of epilepsy subtypes based on structural and functional findings. Furthermore, the role of genetics has become increasingly prominent in epilepsy classification. Genetic discoveries have not only unraveled the molecular underpinnings of various epileptic syndromes but have also provided valuable diagnostic and prognostic insights. This narrative review delves into the expanding realm of genetic testing and its impact on tailoring treatment strategies to individual patients. As the classification landscape evolves, there are accompanying challenges. The narrative review underscores the transformative potential of artificial intelligence and machine learning in epilepsy classification. These technologies hold promise in automating the analysis of complex neuroimaging and genetic data, offering enhanced accuracy and efficiency in epilepsy diagnosis and classification. In conclusion, navigating the shifting landscape of epilepsy classification is a journey marked by progress, complexity, and the prospect of improved patient care. We are charting a course toward more precise diagnoses and tailored treatments by embracing advanced neuroimaging, genetics, and innovative technologies. As the field continues to evolve, collaborative efforts and a holistic understanding of epilepsy's diverse manifestations will be instrumental in harnessing the full potential of this dynamic landscape.

Advancements in Heart Failure Management: A Comprehensive Narrative Review of Emerging Therapies.

Heart failure is a substantial and escalating global health challenge, affecting millions worldwide. This complex syndrome arises from diverse etiologies, encompassing ischemic heart disease, hypertension, valvular abnormalities, and cardiomyopathies. Heart failure is characterized by the heart's inability to pump blood efficiently to meet the body's metabolic demands, leading to debilitating symptoms, frequent hospitalizations, and high mortality rates. Traditionally, the management of Heart failure has focused on alleviating symptoms, reducing fluid retention, and enhancing cardiac contractility. These goals have been achieved through a combination of pharmacological therapies such as angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics, often complemented by device-based interventions like implantable cardioverter-defibrillators and cardiac resynchronization therapy. However, despite these advances, the relentless progression of heart failure remains a significant clinical challenge. Neurohormonal activation, cardiac fibrosis, and cellular remodeling are just a few of the intricate processes contributing to the disease's progression. In recent years, researchers and clinicians have embarked on a quest to identify novel therapeutic approaches that address these underlying mechanisms. One such avenue of exploration involves the revolutionary field of gene therapy, with promising gene-editing techniques, such as CRISPR-Cas9, offering potential routes for correcting genetic mutations that contribute to heart failure. Additionally, regenerative medicine approaches, including stem cell therapy and tissue engineering, hold significant promise for repairing damaged cardiac tissue and restoring function. Furthermore, precision medicine initiatives have gained traction, aiming to tailor heart failure therapies to individual patient profiles, taking into account genetics, biomarkers, and comorbidities. Integrating artificial intelligence and machine learning in heart failure management has also enabled the development of predictive models for early intervention, risk stratification, and personalized treatment recommendations. This narrative review navigates the intricate landscape of emerging therapies for heart failure, emphasizing their potential to revolutionize the field by targeting the disease's fundamental mechanisms. By exploring these innovative approaches, we aspire to provide a comprehensive perspective on the evolving paradigm of heart failure management, fostering a hopeful outlook for patients and clinicians alike.

Revolutionizing Cardiac Care: A Comprehensive Narrative Review of Cardiac Rehabilitation and the Evolution of Cardiovascular Medicine.

Cardiovascular disease (CVD) stands as a global health crisis, with its complex web of conditions, including coronary artery disease, heart failure, hypertension, and stroke, continuing to exact a heavy toll on individuals and healthcare systems worldwide. Despite substantial advances in medical technology and pharmaceutical interventions, CVD remains a formidable adversary, necessitating innovative prevention, management, and rehabilitation approaches. In tracing the historical trajectory of CVD, the narrative reveals the antiquated practices of early 20th-century medicine, marked by extended bed rest as the primary modality for heart-related conditions. It underscores the critical juncture when exercise was first recognized as a therapeutic tool for cardiac health, setting the stage for the evolution of cardiac rehabilitation (CR). CR programs have transcended their initial focus on exercise, expanding to encompass dietary guidance, psychosocial support, and comprehensive risk factor modification. These holistic interventions enhance physical recovery and address the psychosocial and lifestyle aspects of CVD management, ultimately improving patients' overall well-being. CR programs increasingly leverage advanced technologies and personalized strategies to tailor interventions to individual patient needs, ultimately enhancing outcomes and reducing the burden of CVD. In conclusion, this narrative review illuminates the transformative journey of cardiac care, with a particular spotlight on the indispensable role of CR in reshaping the landscape of cardiovascular medicine. By evolving from historical practices to comprehensive, patient-centered interventions, CR has made significant strides in improving the prognosis, quality of life, and holistic well-being of individuals grappling with the complexities of CVD. Understanding this historical context and the contemporary advancements is paramount for healthcare professionals and policymakers as they navigate the intricate terrain of cardiovascular medicine and endeavor to mitigate the impact of this pervasive disease.

Integrative Medicine Approaches: Bridging the Gap Between Conventional and Renal Complementary Therapies.

The global incidence of renal disorders is on the rise, demanding the implementation of novel and comprehensive strategies for patient care. The present study demonstrates the significance of renal health, offering a comprehensive comprehension of renal physiology and the escalating load of renal illnesses. The relevance of controlling renal illnesses is underscored by a thorough examination of conventional treatments, which encompass pharmaceutical interventions, dialysis, and transplantation. Subsequently, the story redirects its attention towards complementary therapies, classifying them into several categories, such as herbal medicine, acupuncture, dietary supplements, and mind-body activities, among various others. This paper presents a comprehensive examination of the available information, providing a critical study of the effectiveness and safety of alternative therapies in renal care. This study focuses on the central idea of integrative medicine, distinguished by its patient-centered and holistic approach and its seamless integration of conventional and complementary therapies. This study examines several integrative care models, using case studies to illustrate successful integrative approaches that have enhanced patient outcomes. The review thoroughly examines the current body of literature on integrative renal care, including meta-analyses, systematic reviews, and notable research discoveries. This study highlights the need for further research to address knowledge gaps and explore areas that require additional examination. These findings emphasize the importance of future research endeavors in this crucial sector. In addition, the paper thoroughly examines the safety issues and regulatory factors pertaining to complementary therapies, underscoring the importance of making educated decisions and maintaining diligent monitoring to safeguard patients' well-being. Integrating patient perspectives, experiences, and shared decision-making is essential to the integrated healthcare process, promoting a collaborative and patient-centered approach. The study culminates by providing a concise overview of the primary discoveries and delineating the ramifications of implementing therapeutic procedures. This statement underscores the considerable potential of integrative medicine in augmenting renal care, ultimately leading to enhanced patient outcomes and an improved overall quality of life for persons with renal diseases. Also, this literature review provides a thorough and knowledgeable examination of the incorporation of conventional and complementary therapies in the context of renal health. It gives valuable perspectives for healthcare practitioners, researchers, and policymakers interested in enhancing care strategies for individuals with renal conditions.

The Changing Global Epidemiology of Re-emerging Human Monkeypox Virus Infection: A Systematic Review.

Human monkeypox virus (MPVX) infection represents an emerging zoonotic disease caused by an orthopoxvirus, resulting in a condition reminiscent of smallpox. More recent developments have witnessed a notable surge in global MPVX outbreaks, eliciting significant concerns. We aimed to investigate the epidemiological factors of the emerging human monkeypox virus infection, including the number of suspected, confirmed, and fatal cases, as well as the risk factors for contracting monkeypox infection. We performed a systematic review of peer-reviewed literature by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic database search (PubMed, Wiley Online Library, and Science Direct) was undertaken. For monkeypox-related studies, we included 25 peer-reviewed articles from 2018 and 2022, and data were extracted on the current evidence on the cases and the risk factors for MPVX infection, to develop public health advisories. Our reports show a rapid rise of MPVX cases in the highly endemic African regions after the 1970s, spread to other countries, and an increase in the median age from young children to young adults. The cessation of smallpox vaccination might have been one of the factors responsible for these findings. As of 2022, the genomic sequences of ten MPVX strains associated with the recent countrywide outbreak have been determined. While the West African Clade has been primarily implicated in the recent viral surge, data were insufficient to determine which mutation contributed to increased transmissibility. In the Democratic Republic of the Congo (DRC), sleeping on the floor was significantly associated with contracting MPVX, while eating or processing of animal foods was not a significant risk factor. In the United States, cleaning the cages and bedding of sick animals, touching infected animals, and daily exposure to sick animals were associated with an increased probability of contracting the MPVX infection. Recent global outbreaks and the rising incidence of MPVX infections among young adults in the endemic zones might be a result of the cessation of the smallpox vaccine. The increased risk associated with exposure to sick animals or sleeping on the floor suggests high infectivity from animal excretions. Increasing awareness, strict surveillance, and contact tracing can help contain global outbreaks. The ring vaccination approach for exposed individuals is another potential disease containment strategy. Future studies should investigate measures for rapid laboratory diagnosis, maintaining lab safety, and transmissibility.

Digital Pathology: Transforming Diagnosis in the Digital Age.

In the context of rapid technological advancements, the narrative review titled "Digital Pathology: Transforming Diagnosis in the Digital Age" explores the significant impact of digital pathology in reshaping diagnostic approaches. This review delves into the various effects of the field, including remote consultations and artificial intelligence (AI)-assisted analysis, revealing the ongoing transformation taking place. The investigation explores the process of digitizing traditional glass slides, which aims to improve accessibility and facilitate sharing. Additionally, it addresses the complexities associated with data security and standardization challenges. Incorporating AI enhances pathologists' diagnostic capabilities and accelerates analytical procedures. Furthermore, the review highlights the growing importance of collaborative networks facilitating global knowledge sharing. It also emphasizes the significant impact of this technology on medical education and patient care. This narrative review aims to provide an overview of digital pathology's transformative and innovative potential, highlighting its disruptive nature in reshaping diagnostic practices.

Unveiling the Mysteries of Long COVID Syndrome: Exploring the Distinct Tissue and Organ Pathologies Linked to Prolonged COVID-19 Symptoms.

The ongoing battle against the coronavirus disease 2019 (COVID-19) pandemic has encountered a complex aspect with the emergence of long COVID syndrome. There has been a growing prevalence of COVID-19-affected individuals experiencing persistent and diverse symptoms that extend beyond the initial infection phase. The phenomenon known as long COVID syndrome raises significant questions about the underlying mechanisms driving these enduring symptoms. This comprehensive analysis explores the complex domain of long COVID syndrome with a view to shed light on the specific tissue and organ pathologies contributing to its intricate nature. This review aims to analyze the various clinical manifestations of this condition across different bodily systems and explore potential mechanisms such as viral persistence, immune dysregulation, autoimmunity, and molecular mimicry. The goal is to gain a better understanding of the intricate network of pathologies contributing to long COVID syndrome. Understanding these distinct pathological indicators provides valuable insights into comprehending the complexities of long COVID and presents opportunities for developing more accurate diagnostic and therapeutic strategies, thereby improving the quality of patient care by effectively addressing the ever-changing medical challenge in a more focused manner.

A Narrative Review on the Monkeypox Virus: An Ongoing Global Outbreak Hitting the Non-Endemic Countries.

Monkeypox is a rare zoonotic DNA with lineage from the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. With a previous history of controlled and contained occasional outbreaks of the virus, currently, a widely erupted outbreak of monkeypox with progressively rising numbers has been reported since May 2022 in multiple countries of the western hemisphere that are not historically endemic for this infection, particularly the United Kingdom and European Union countries. We have written a comprehensive review article to help clinicians better understand the disease. The global cessation of smallpox vaccination has been hypothesized to cause the rise in monkeypox infections in recent years. Monkeypox, like any other viral infection, commences with prodromal symptoms; a maculopapular rash with centrifugal distribution usually follows. Polymerase chain reaction (PCR) confirms the diagnosis. Transmission in humans is possible through infected animals or humans. In the ongoing 2022 outbreak, the monkeypox virus has been undergoing novel mutations at an alarming rate. Treatment options for monkeypox are an area that still requires extensive research, and the utility of certain antiviral medications in treating monkeypox infection is currently being explored but is still controversial and debatable.

Exploring the Effectiveness and Safety of Azilsartan-Medoxomil/Chlorthalidone Versus Olmesartan-Medoxomil/Hydrochlorothiazide in Hypertensive Patients: A Meta-Analysis.

This study aims to assess the effectiveness and safety of azilsartan-medoxomil/chlorthalidone (AZI-M/CT) compared to olmesartan-medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with hypertension. Systematic searches were conducted on PubMed, Google Scholar, and ClinicalTrials.gov, starting from their establishment until March 15, 2023. The purpose of these searches was to locate original reports that compare the effectiveness of AZI-M/CT and OLM/HCTZ in treating hypertension. Data on various characteristics at the beginning and end of the studies were gathered. The analyses were carried out using Review Manager 5.4.1 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Odense, Denmark) and STATA 16.0 software (Stata Corp. LP, College Station, TX, USA). Risk ratios (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated as part of the study. A total of 3,146 individuals from four separate investigations were included in the study, with 1,931 individuals receiving AZI-M/CT and 1,215 individuals receiving OLM/HCTZ. The combined analysis revealed that the average diastolic blood pressure (DBP) was significantly lower in the AZI-M/CT group compared to the OLM/HCTZ group (WMD -2.64 [-2.78, -2.51]; P = 0.00001; I2 = 1%). However, there were no significant differences in mean systolic blood pressure (SBP; WMD -2.95 [-6.64, 0.73]; P = 0). Furthermore, the AZI-M/CT group had a notably higher incidence of major adverse events (RR 1.58 [1.20, 2.08]; P = 0.001; I2 = 11%) and any treatment-emergent adverse events (RR 1.11 [1.03, 1.20]; P = 0.007; I2 = 51%). However, there was no significant difference in the mortality risk between the two groups (RR 0.74 [0.14, 3.91]; P = 0.72; I2 = 0%). Based on the results of our meta-analysis, AZI-M/CT is more effective than OLM/HCTZ at reducing blood pressure in elderly hypertensive patients. However, because of the small sample size, favorable results must be carefully reevaluated, and more studies are needed.

Recurrent Primary Peritoneal Psammocarcinoma: A Case Report on a Diagnostic Challenge in Cytology.

Psammocarcinoma (PCa) is a rare variant of low-grade papillary serous carcinoma that can arise from the peritoneal as well as ovarian surfaces. When this tumor involves the extra-ovarian peritoneum significantly and the ovarian surface minimally or not at all, it is considered of peritoneal origin. PCa has a recurrent indolent clinical course. It is challenging to diagnose peritoneal PCa, particularly on cytological smears because of the bland cellular features of neoplastic cells. We report a case of recurrent metastatic primary peritoneal PCa in a 71-year-old female of Ashkenazi Jewish ancestry diagnosed on cytology of ascitic and cystic fluid.

Public Knowledge About COVID-19 Booster Vaccines in Pakistan: A Study Conducted in a Tertiary Care Hospital in Karachi.

The coronavirus disease 2019 (COVID-19) pandemic has deteriorated the healthcare system and economy worldwide. Globally, by making the primary vaccination against the coronavirus necessary, the surge in cases waned, but as the effects of this vaccination decreased after some time, to prevent another pandemic, vaccination was still necessary. As a result, receiving a COVID-19 booster shot can boost immunity against the coronavirus. This study aimed to assess knowledge of COVID-19 booster vaccines in Pakistan among the general public and understand the factors affecting the vaccination process in the state. In this cross-sectional study, non-probability convenience sampling was done. Its physical data collection was conducted in September 2022 in a tertiary care hospital in Karachi, Pakistan. Data were collected from 384 individuals who visited the hospital with consent before filling out the questionnaire. The mean age of respondents was 35.81 (standard deviation (SD) = ±13.006), and 98.7% of individuals were primarily vaccinated for COVID-19, but out of these, only 60.1% received the booster jab. The most commonly reported side effects of primary doses of COVID-19 and its booster were pain at the injection site, fatigue, and fever, but these effects did not appear to have as much of an impact on the vaccination process as education did. The results are evident that out of primarily vaccinated individuals against COVID-19, 40.16% are reluctant to receive its booster. Therefore, it is essential to create awareness among the masses about vaccination and its importance.

Cannabinoid-Associated Hyperemesis Syndrome Treated With Dronabinol: Killing a Poison With the Poison.

Cannabinoid hyperemesis syndrome (CHS) is a medical condition characterized by recurrent nausea, vomiting, and abdominal pain in individuals who frequently use cannabis. This case report highlights the successful treatment of CHS using dronabinol, a synthetic cannabinoid compound. A 21-year-old female presented with severe abdominal symptoms, including vomiting and pain, alongside a history of chronic cannabis use. Despite initial symptomatic treatment, her symptoms persisted. After being diagnosed with CHS, the patient was administered one dose of haloperidol, which led to agitation and worsening of her symptoms. Eventually, she was given one dose of dronabinol resulting in significant symptom improvement. Subsequent doses of dronabinol led to the complete resolution of her CHS symptoms. This case underscores the importance of thorough history-taking, especially for complex patients. Also, with cannabis legalization, cases of CHS are on the rise, and widespread awareness is vital for healthcare practitioners to recognize and appropriately manage nausea and vomiting induced by long-term cannabis intake. Although this case provides valuable insights, its limitations emphasize the need for further research to establish evidence-based guidelines for CHS management.

Consequences of a Missed History: A Case of Antidepressant Discontinuation Syndrome.

Antidepressant discontinuation syndrome (ADDS) is reported to occur in almost 30-50% of the patients who take antidepressants for a duration of at least four to six weeks and then suddenly discontinue the drug. Since there is an increase in the use of antidepressants for various reasons by general practitioners, patient education about when and how to discontinue a drug is not acknowledged enough. It is reported to occur with the use of different classes of antidepressants - selective serotonin reuptake inhibitor (SSRI), monoamineoxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), and atypical antipsychotics like risperidone, trazodone, clozapine, and venlafaxine. Slow tapering off the drugs has also caused ADDS. Symptoms start within two to four days of quitting the drug and are usually mild lasting for two to four weeks (can persist for six to 12 months) but could be severe enough leaving the patient nonambulatory. Here, we represent a case of a 55-year-old female who presented to the outpatient clinic with complaints of headache, vomiting, and diarrhea. The patient had 10 to 12 episodes of watery diarrhea every day and bilateral, continuous, pressing headache associated with multiple episodes of non-projectile vomiting. She was investigated for ultrasound sonography (USG) abdomen, CT head, and lab investigations which turned around to be normal. A follow-up visit with detailed history revealed she suddenly stopped taking escitalopram after six months by herself without tapering off the dose, two days before the onset of symptoms. Escitalopram was reinstated and the symptoms started to resolve in two to three days. All the unnecessary investigations and treatment could have been prevented if the proper history was taken and revealed at the initial visit.

Therapeutic Strategies for Human Epidermal Receptor-2 Positive Metastatic Breast Cancer: A Literature Review.

Breast cancer is a frequently occurring malignancy in women. Immunologically, breast cancers can be classified into four subtypes depending on the types of receptors present and their expression profiles. These are estrogen positive, progesterone positive, human epidermal growth factor receptor type 2 (HER2) positive, and triple-negative as identified by immunohistochemistry. This classification is the basis of response to treatment, prognosis, and survival. With the identification of HER2 receptor overexpression, targeted therapies with anti-HER2 agents have been developed. The first-line therapy approved for HER2 positive tumors is trastuzumab and pertuzumab linked to taxane and further treatment with an antibody-drug conjugate to achieve satisfactory outcomes. Tyrosine kinase overexpression can be treated with lapatinib, which has also been approved for improving survival and is used in combination with capecitabine. Acquired resistance in HER2 positive tumors is shown in many cases due to genetic or epigenetic modifications. Therefore, it is very important to plan therapeutic strategies and design effective treatment approaches. For a long time, only two agents, trastuzumab and lapatinib, have been approved by the Food and Drug Administration (FDA) for the treatment of HER2 positive breast cancers. There has been no appropriate treatment for trastuzumab resistance and its failure to reduce tumor growth. Lapatinib was approved by the FDA in 2007 for HER2 positive breast cancer. Three existing therapy options after trastuzumab resistance was proposed by clinicians: continuation of trastuzumab, starting therapy with lapatinib, and the synergistic use of trastuzumab and lapatinib. There have been several effective therapies proposed for HER2 positive breast cancers in correlation with clinical trials. Discovering the mechanisms of trastuzumab resistance would increase its response to therapy and better clinical outcome. Clinicians are being continuously challenged by the resistance mechanisms and bioavailability of the drugs in the treatment of metastatic breast cancers. The addition of new drugs to the chemotherapeutic regimen increases the complexity, burden of side effects, and chances of relapse. Novel anti-HER2 agents have been directed towards therapy making a major paradigm shift.