Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. DATA SOURCE: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. DATA SUMMARY: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. CONCLUSION: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

Audit to optimize antibiotics use in neonatal septicemia.

Objectives: To assess appropriate antibiotics use in neonatal sepsis and to highlight the need for developing an Antibiotic stewardship program at local levels. Methods: A clinical audit was conducted in the neonatal ward of the tertiary care hospital of Lahore for one year from May 2019 to May 2020. Reports of blood culture and drugs susceptibility were gathered from the microbiology department, and clinical records were evaluated about the choice of the antimicrobials, dosage, frequency, and clinical prognosis. The statistics were applied using SPSS software. Results: Eighty five neonates with the mean age of five days were treated in tertiary care hospital for septicemia. Every patient received more than one antibiotic empirically. The most prescribed drug combination (90.6%) was Cefotaxime and Amikacin. Optimum antibiotics dose was prescribed in only 70.2% of cases. Blood isolates showed gram-negative bacilli in 69 (81.2%) cases, gram positive cocci in 14 (16.5%) cases, two (2.3%) culture susceptibility reports showed growth of candida. Gram negative organisms were most susceptible to Imipenem (54%), Piperacillin-Tazobactam (48%) and Gentamicin (48%). Gram-positive organisms showed the most susceptibility to Vancomycin (100%), Amikacin (92%), and Co-amoxiclav (85%). Meropenem (39%), Linezolid (28%), and Vancomycin (27%) were the most commonly given alternate antibiotics. All the patients (n=10, 11.8%) whose culture sensitivity reporting showed susceptibility to empirical therapy survived. Conclusion: Due to poor availability of latest data about local antibacterial resistance pattern and lack of knowledge among pediatricians about latest antibiotic prescribing protocols, many inconsistencies were noted in the use of antibiotics in neonatal sepsis which resulted in a poor outcome hence, reflecting in international key health indicators (neonatal mortality rate) of country. Concerning the change in the resistance pattern of microorganisms to antimicrobials, it is high time to collect local data about antibacterial susceptibility and develop an antibiotic stewardship program to stop inappropriate use of antibiotics.

Electrifying Consequences: Posterior Reversible Encephalopathy Syndrome After an Electric Shock Injury.

Reversible posterior leukoencephalopathy syndrome, often referred to as posterior reversible encephalopathy syndrome (PRES), is a disorder characterized by acute cerebral dysfunction and is seen in conjunction with vasogenic edema on brain imaging. Headaches, visual issues, seizures, abnormal mentation, disturbances in awareness, and focal neurological symptoms are its defining features. In this case report, we present a 40-year-old male patient who developed PRES after experiencing a high-voltage electric shock.

Assessing the Utility of the Aspartate Aminotransferase to Platelet Ratio Index (APRI) as a Noninvasive Indicator for Liver Cirrhosis.

Background Of liver-related disorders, cirrhosis is currently the leading cause of death and has become a significant global public health concern. Aspartate aminotransferase to platelet ratio index (APRI), a newer prognostic modality, is a very effective noninvasive diagnostic for identifying advanced liver fibrosis. Methods A prospective observational study was conducted among individuals with liver disease, 100 cases and 100 controls for two years. All the sociodemographic details, clinical features of the patients, and clinical findings such as prothrombin time (PT), liver function tests, kidney function tests, and total blood count were recorded using a pretested semi-structured questionnaire. Results According to our survey results, 48% of the participants were between the ages of 40 and 60. Regarding aPTT (activated partial thromboplastin time) and liver function test characteristics (serum glutamic-oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase (SGPT)), we showed a substantial difference between the patients and controls. Regarding the APRI distribution, we also found a statistically significant variation between the research groups. When we compared the validity of APRI scores in diagnosing cirrhosis, we discovered that the ideal cutoff value of APRI was determined to be 3.99, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33%, 86%, 70%, and 56%, respectively. The area under the receiver operating characteristic (ROC) curve for APRI in detecting cirrhosis was also 0.693. Conclusion Thus, our study results conclude that APRI is a crucial noninvasive prognostic tool that can be utilized to prognostize liver cirrhosis.

Clinical Presentation, Tumor Characteristics, and Management of Intradiverticular Transitional Cell Carcinoma of the Urinary Bladder: A Systematic Review.

Intradiverticular transitional cell carcinoma (TCC) of the bladder poses unique challenges due to its presentation within the bladder diverticula. This review synthesizes current knowledge on the diagnosis and management of this condition, emphasizing the need for early detection to optimize patient outcomes. The literature underscores the importance of tailored treatment strategies, ranging from radical surgeries to adjuvant chemotherapy, to combat the aggressive nature of intradiverticular TCC. Additionally, stringent post-treatment surveillance protocols are vital in addressing high recurrence rates. Future research directions include biomarker identification, comparative efficacy studies of treatment modalities, and the exploration of innovative therapeutic approaches such as immunotherapy. Longitudinal studies analyzing patient outcomes will provide valuable insights into survival rates and quality of life post-treatment, informing future clinical guidelines. This comprehensive review aims to enhance understanding and management strategies for intradiverticular TCC, paving the way for improved patient care and outcomes in this challenging form of bladder cancer.

Efficacy of Atezolizumab Plus Bevacizumab Versus Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma: a Meta-analysis.

INTRODUCTION: Hepatocellular carcinoma is a lethal disease and there has been a debate regarding the first-line treatment of its advanced and unresectable form. Observational studies have explored atezolizumab plus bevacizumab versus lenvatinib, yielding mixed results. This systematic review and meta-analysis aim to compare efficacy and safety of both treatment arms. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines. Randomized control trials, cohort studies, or case-control that included patients above age 60 with unresectable hepatocellular carcinoma confirmed by radiological imaging were included. At least one of the outcomes: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response, or adverse events was included in the selected studies. RESULTS: Ten cohorts were included in the analysis with a total of 6493 patients. Nine of the included studies had patients with advanced HCC (BCLC-C) or intermediate HCC (BCLC-B) and 1 study included patients with all three stages (BCLC-A, BCLC-B, and BCLC-C). Of these patients, 2524 patients received atezolizumab plus bevacizumab (A + B) combination while 3969 received lenvatinib. The overall survival was better statistically in the A + B group then the lenvatinib group (MD: - 5.06; 95% CI: - 7.79 to - 2.33; p = 0.0003, I2 = 0%). The progression-free survival was significantly improved in A + B arm as well group (MD: - 4.96; 95% CI: - 7.67 to - 2.26; I2 = 0%, p = 0. 0003). There was no significant difference in objective response rate, disease control rate, and frequency of adverse events in either of the group. CONCLUSION: Our study concluded that combination therapy with atezolizumab plus bevacizumab could increase the survival duration without affecting the disease course. Moreover, while the severity of adverse events was greater in the A + B group, their frequency was comparable to the lenvatinib group.

COVID-19 Testing Crisis Management Through a Public-Private Partnership in Sindh, Pakistan.

As the coronavirus disease (COVID-19) pandemic spread, meeting the testing needs to control the spread of infection became a major challenge worldwide. In Pakistan, the lack of the requisite infrastructure and training compounded the acute shortage of testing kits and other consumables. Against this backdrop and to urgently improve province-wide access to high-quality COVID-19 polymerase chain reaction (PCR) testing with rapid turnaround times, the Government of the Sindh (GoS) province of Pakistan entered into a public-private partnership with Indus Hospital & Health Network (IHHN). Under this partnership, the GoS undertook sample collection and Indus Hospital in Karachi, Sindh, centralized testing. We describe the implementation strategies adopted by the partnership, as well as the challenges, opportunities, and lessons learned. Notably, up to 40% and 22% of total COVID-19 PCRs done in Sindh in the first 2 months of the pandemic, respectively, were performed at Indus Hospital in Karachi, though this percentage declined gradually as other centers caught up with their testing capacities. The rapid scaling up was achieved through a combination of mechanisms and factors including building on preexisting partnerships between the GoS and IHHN, pooling resources and harnessing distinct and complementary roles, relocating existing resources, introducing automation and information technology system changes, establishing risk mitigation strategies, and introducing quality measures within testing processes. The primary outcome of the partnership was rapid province-wide access to quality COVID-19 PCR testing with short turnaround times and at no cost to the patient. Furthermore, implementation of the partnership goals established new mechanisms as well as strengthened existing ones to enable rapid response to the future global health security challenges in Sindh, Pakistan.

Efficacy and Toxicity Profile of Carfilzomib-Based Regimens for Treatment of Newly Diagnosed Multiple Myeloma: A Systematic Review.

Carfilzomib (CFZ) is a proteasome inhibitor currently approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Multiple trials are ongoing to evaluate its efficacy and safety in newly diagnosed multiple myeloma (NDMM). The use of CFZ-based two- or three-drug combination regimens as induction for the management of NDMM is an emerging approach. CFZ-based regimens include combinations of immunomodulators, alkylating agents, and monoclonal antibodies along with dexamethasone. In this review, we assess the efficacy and toxicity of CFZ-based regimens in NDMM. We reviewed a total of 27 studies (n=4538 patients) with overall response rates (ORR) ranging between 80% and 100%. Studies evaluating the combination of CFZ with daratumumab reported an ORR of approximately 100%. Achievement of minimal residual disease (MRD) negativity, measured by multi-parameter flow cytometry (MPFC), ranged between 60% and 95% in 4 (n=251) out of 6 studies that measured MRD-negativity. The interim results of the ENDURANCE trial failed to show superior efficacy and progression-free survival (PFS) of carfilzomib-lenalidomide when compared to bortezomib-lenalidomide combination, albeit with a lower incidence of neuropathy. Hematological toxicity was the most common adverse event observed with these regimens, and the most common non-hematological adverse events were related to cardiovascular and electrolyte disturbances. We need to further evaluate the role of CFZ in NDMM by conducting more Phase III trials with different combinations.

Acute Myeloid Sarcoma: An Unusual Cause of Diarrhea.

A 62-year-old man with a past medical history of hypothyroidism was admitted for diarrhea and abdominal pain for three weeks. Initial workup for diarrhea was negative. His condition deteriorated after hospitalization. He underwent sigmoidoscopy which showed rectosigmoid mucosal ulceration. Pathology showed leukemic cells infiltration of the mucosa. The patient underwent bone marrow biopsy which confirmed the diagnosis of acute myeloid leukemia (AML). He received induction chemotherapy and his symptoms improved.

Adverse Effects of Caffeine on Development of Femur of BALB/c Mice and Protective Role of Vitamin D3.

OBJECTIVE: To determine the effects of caffeine ingestion on the development of femur and role of vitamin D3 in preventing these effects in BALB/c mice. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Anatomy, Army Medical College, Rawalpindi, in cooperation with NIH (National Institute of Health), Islamabad, from October 2014 to October 2015. METHODOLOGY: Thirty (100%) BALB/c mice, 50% male and female each, three weeks old, weighing 12-14 grams were taken and divided equally and randomly into three groups, each having 10 (33.3%) mice; 5 (16.6%) male and female. G1 (control group) was given normal diet with water ad libitum. G2and G3(experimental groups) were given 10 mg of caffeine per 100g body weight, three days a week, through oral gavage for 60 days on alternate days. However, experimental group G3was additionally provided 0.1µg vitamin D3daily, through oral gavage for 60 days. Experimental groups were compared with control group and data was analyzed statistically. RESULTS: The mean weight of mice femur of G1(control group) was 0.387 ±0.019 g; while mean weights of right femur of G2and G3(experimental groups) were 0.316 ±0.020 g and 0.345 ±0.020 g, respectively. Similarly, mean right femur length of group G1 was 20.70 ±0.609 mm; while for groups G2 and G3, it was 24.382 ±1.087 mm and 22.966 ±0.822 mm, respectively. In comparison with group G1for groups G2and G3, femur weight decreased, however femur length increased. CONCLUSION: Caffeine intake caused femur length to increase and weight to decrease, but treatment with vitamin D3.