Occurrence of toxic elements in river areas along drains and groundwater resources: source of contamination and associated health risk.

The objective of the current research was to examine the water quality of the River Ravi and the River Sutlej, with a specific focus on potentially toxic elements (PTEs). Additionally, we sought to monitor the sources of pollution in these rivers by gathering samples from the primary drains that carry industrial and municipal waste into these water bodies. Furthermore, we aimed to evaluate the impact of PTEs in surface water on groundwater quality by collecting groundwater samples from nearby populated areas. A total of 30 samples were collected from these three sources: rivers (6 samples), drains (9 samples), and groundwater (15 samples). The analysis revealed that the levels of PTEs in the samples from these three resources having a mean value: arsenic (As) 23.5 µg/L, zinc (Zn) 2.35 mg/L, manganese (Mn) 0.51 mg/L, lead (Pb) 6.63 µg/L, and chromium (Cr) 10.9 µg/L, exceeded the recommended values set by the World Health Organization (WHO). Furthermore, PTEs including (As 84%), (Zn 65%), (Mn 69%), (Pb 53%), (Cr 53%), and (Ni 27%), samples were beyond the recommended values of WHO. The results of the Principal Component Analysis indicated that surface water and groundwater exhibited total variability of 83.87% and 85.97%, respectively. This indicates that the aquifers in the study area have been contaminated due to both natural geogenic factors and anthropogenic sources. These sources include the discharge of industrial effluents, wastewater from municipal sources, mining activities, agricultural practices, weathering of rocks, and interactions between rocks and water. Spatial distribution maps clearly illustrated the widespread mobilization of PTEs throughout the study area. Furthermore, a health risk assessment was conducted to evaluate the potential adverse health effects of PTEs through the ingestion of drinking groundwater by both children and adults. Health risk assessment result show the mean carcinogenic values for As, Cr, Pb and Ni in children are calculated to be (1.88E-04), (2.61E-04), (2.16E-02), and (5.74E-05), respectively. Similarly, the mean carcinogenic values for the above mentioned PTEs in adults were recorded to be (2.39E-05), (3.32E-05), (1.19E-03), and (7.29E-06) respectively. The total hazard index values for As, Zn, Cr, Pb, Mn, Cu, and Ni in children were observed to be (9.07E + 00), (9.95E-07), (4.59E-04), (5.75E-04), (4.72E-05), (2.78E-03), and (5.27E-05) respectively. The analysis revealed that As has an adverse effect on the population of the study area as compared to other PTEs investigated in this study.

Tirzepatide: A novel cardiovascular protective agent in type 2 diabetes mellitus and obesity.

Cardiovascular disease (CVD) remains a major global health concern, and obesity and diabetes mellitus have been found to be important risk factors. Tirzepatide a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1) receptor agonist has been shown to have cardioprotective effects. Noteworthy benefits of Tirzepatide include decreased cardiovascular risk factors in people with Type 2 diabetes mellitus (T2DM). In the SURPASS-4 trial, tirzepatide significant decreased blood pressure, body weight, and HbA1c. Furthermore, the SURMOUNT-1 trial demonstrated the effectiveness of tirzepatide in reducing cardiometabolic risk factors in people with obesity without T2DM. Together, the dual receptor agonism improves lipid profiles, increases insulin secretion, reduces inflammation, and promotes endothelial integrity. Tirzepatide shows promise as a comprehensive therapeutic option for managing cardiovascular risk factors in patients with T2DM and obesity. While further studies are needed to assess the long-term cardiovascular benefits, current evidence supports tirzepatide's potential impact on cardiovascular health beyond its antidiabetic properties.

Point-of-care ultrasound is a useful adjunct tool to a clinician's assessment in the evaluation of severe hyponatraemia.

INTRODUCTION: Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients. METHODS: Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge. RESULTS: n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases. CONCLUSION: As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

Characterization of Root and Foliar-Applied Iron Oxide Nanoparticles (α-Fe2O3, γ-Fe2O3, Fe3O4, and Bulk Fe3O4) in Improving Maize (Zea mays L.) Performance.

Iron (Fe) oxide nanoparticles (NPs) improve crop growth. However, the comparative effect of root and foliar-applied different sources of Fe oxide NPs on plant performance at morphological and physiological levels still needs to be discovered. In this study, we characterized the growth and physiological responses of hydroponic-cultured maize seedlings to four sources of Fe (i.e., α-Fe2O3, γ-Fe2O3, Fe3O4 NPs, and bulk Fe3O4) and two application methods (root vs. foliar). Results showed that Fe concentration in root and shoot increased by elevating the level of NPs from 100 mg L-1 to 500 mg L-1. Overall, the responses of maize seedlings to different sources of Fe oxide NPs were as follows: Fe3O4 > γ-Fe2O3 > α-Fe2O3 > bulk Fe3O4. The application of Fe at concentrations ranging from 100 mg L-1 to 500 mg L-1 had no significant effects on various growth parameters of maize, including biomass, chlorophyll content, and root length. Iron oxide NPs increased the plant biomass by 23-37% by root application, whereas it was 5-9% by foliar application. Chlorophyll contents were increased by 29-34% and 18-22% by foliar and root applications, respectively. The non-significant response of reactive oxygen species (i.e., superoxide dismutase, catalase, and peroxidase) suggested optimum maize performance for supplementing Fe oxide NPs. A confocal laser scanning microscope suggested that Fe oxide NPs entered through the epidermis and from the cortex to the endodermis. Our results provide a scientific basis that the root application of Fe3O4 at the rate of 100 mg L-1 is a promising approach to obtain higher maize performance and reduce the quantity of fertilizer used in agriculture to minimize environmental effects while improving crop productivity and quality. These findings demonstrated the tremendous potential of Fe NPs as an environmentally friendly and sustainable crop approach.

Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Limited data comparing prasugrel and ticagrelor in acute coronary syndrome are available. Online databases, including MEDLINE and Cochrane Central, were queried to compare these drugs. The primary outcomes of this meta-analysis are myocardial infarction (MI), all-cause mortality, cardiovascular mortality, noncardiovascular mortality, stent thrombosis, and stroke. The secondary outcome is major bleeding. A total of 9 studies, including 94,590 patients (prasugrel group = 32,759; ticagrelor group = 61,831), were included in this meta-analysis. The overall mean age was 62.73 years, whereas the mean age for the ticagrelor and prasugrel groups was 63.80 and 61.65 years, respectively. Prasugrel is equally effective as compared with ticagrelor in preventing MI. There was no difference between the 2 groups regarding all-cause mortality, stent thrombosis, stroke, or major bleeding. In patients with acute coronary syndrome, prasugrel is equally effective when compared with ticagrelor in preventing MI.

Coronary Intra-orbital Atherectomy Complications and Procedural Failure: Insight From the Manufacturer and User Facility Device Experience (MAUDE) Database.

BACKGROUND: The Diamondback 360® Coronary Orbital Atherectomy System (Cardiovascular Systems Inc., St. Paul, MN) is the first and only orbital atherectomy system approved by the US FDA for the treatment of severely calcified lesions. While the device has proven to be safe in clinical trials, real-world data are minimal. METHODS: The Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports on the Diamondback 360® Coronary from January 2019 to January 2022. RESULTS: A total of 566 events were reported during the study period. After the exclusion of duplicate reports, the final cohort included 547 reports. The most common mode of failure was break or separation of a device part (40.4%, n = 221) mainly due to breaking in the tip of the ViperWire (66.1%), driveshaft (22.7%), or crown (12.2%). The most common vessel associated with events was the left anterior descending artery (31.4%), followed by the right coronary artery (26.9%), left circumflex (21.6%), and left main coronary artery (6.4%). The most common clinical adverse outcome was perforation (33.0%, n = 181) with 23.7% resulting in cardiac tamponade. Most perforation cases were treated by covered stent (44.2%), surgery (30.5%), stent (98%), and balloon angioplasty (9%). There were 89 (16.3%) events of death with 67% due to perforation (p < 0.001). CONCLUSION: Our study provided a glimpse of real-world adverse outcomes and common modes of failure due to orbital atherectomy. The most common mode of failure was the break or separation of a device part and the most common complication was perforation according to the MAUDE database. It will help physicians to anticipate complications and escalate care appropriately.

Pharmacotherapeutic options for pancreatic ductal adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED: PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION: Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.

Inventorization of traditional ethnobotanical uses of wild plants of Dawarian and Ratti Gali areas of District Neelum, Azad Jammu and Kashmir Pakistan.

BACKGROUND: An ethnobotanical expedition was conducted to document the traditional ethnobotanical (TEB) uses of wild flora of Dawarian and Ratti Gali villages of District Neelam, Azad Jammu and Kashmir (AJK) Pakistan. District Neelam has rich plant diversity and is hub of many endemic plant species while the study areas are not yet explored. The research area: Dawarian and Rati Gali (DRG) area is mountaineous terrain and villages are located on far and farther distances. DRG area has rich biocultural and plant diversity comprising of different ethnic groups of Kashmir state. The current research was aimed to explore and document traditional medicines (TEMs) and other domestic and commercial uses of wild plants. This study will assist to evaluate conservation and commercial worth of wild flora which can be potential candidate for drug discovery through ethnopharmacological analysis. METHODS: The current quantitative ethnobotanical research was carried out in 2018 by interviewing 150 indigenous informants (90 male and 60 female) of DRG area using questionnaire applying structured and semi structured interview methodology. Data analysis was analyzed by using quantitative ethnobotanical statistical tools such as fidelity level (FL), informant consensus factor (ICF), Spearman's rank correlation (SRC) and data matrix ranking (DMR). RESULTS: The indigenous people of DRG area use wild plants in their daily life to cope life necessities i.e. food, vegetables, fodder, fuel, shelter, timber and herbal medicines. TEMs are primarily used to cure different infirmities like diabetics, asthma, dysentery, constipation, cold, fever, joint pain, wound healing, cancer, cardiovascular disorders, epilepsy, kidney infections and many types of skin diseases. Current study revealed the data of 103 wild plants species belonging to 46 plant families from selected areas of District Neelum, AJK. Results depicted that Asteraceae ranked 1st (12 plants spp). Among plant parts used leaf ranked 1st (18%), followed by seed (17%) and root (13%). While prevalent form recipe mode was decoction (20%), followed by powder (17%) and extract (14%) and fodder was highest (37%) EB use-form fodder, followed by food (32%) and fuel (17%). Quantitative ethnobotanical analysis (QEA) was carried to find the reliability and novelty of the study. Five plant species including Berberis lyceum (FL = 97.78%), Isodon rugosus (FL = 95.71%), Saussurea lappa (FL = 94.74%), Aconitum heterophyllum (FL = 92.71%) and Taxus baccata (91.58%) had shown high fidelity level which confirmed that these plants have high medicinal worth in study area. The highest value (0.94) of ICF was for diseases group "tuberculosis and leucorrhea", followed by stomachache and flatulence (0.93), diabetics and blood pressure (0.92) and asthma and chest infections (0.88). For other uses fuel with ICF (0.83) ranked first and second was hedging and thatching (ICF = 0.82) where people use plants or their parts for construction. Spearman's rank correlation (SRC) test indicated that number of TEB uses increases if number of species is increased. Jaccard index (JI) analysis depicted that 56.31% plants are being used as TEMs which are first time explored from the study area. While 26.21% plants are being used in different TEB uses which are different from past cited literature. These novel findings of research indicate that wild flora of the study area has great potential for novel drug discovery and provision of materialist services for the indigenous communities. CONCLUSION: The present research revealed that TEMs uses of 58 plants are novel being first time reported from the study area (DRG) of District Neelam of AJK. The results showed that plants like Acer cappadocicum, Ajuga bracteosa and Swertia paniculata are used to cure diabetes, Viscum album, Viola canescens, Taxus baccata are used for cure of cancer, Isodon rugosus, Polygala chinensis are used in TEMs for treating cardiovascular disorders and Anaphalis triplinervis is used for epilepsy. Berberis lyceum, Ajuga bracteosa, Aconitum heterophyllum, Bistorta amplexicaule, Saussurea lapa and Jurinea dolomiaea are severely threatened and there is urgent need to do conservation measures for available of valuable MPs to the indigenous communities for life necessities and for future research. The current study will also be useful addition in ethnobotanical database, preservation of traditional culture and drug discovery and drug development through future ethnopharmacological research.

Management of Relapsed Hairy Cell Leukemia: A Systematic Review of Novel Agents and Targeted Therapies.

BACKGROUND: Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL. METHODS: Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: "hairy cell leukemia" or "leukemia, hairy cell" AND "relapse" or "recurrence". We included only prospective clinical trials with outcome data. RESULTS: Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated. CONCLUSION: Novel agents have good efficacy in HCL in patients with multiple relapses.

A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors.

Chimeric antigen receptor T (CAR-T) cell therapy utilizes patients' own T lymphocytes that are engineered to attack cancer cells. It is Food and Drug Administration (FDA)-approved in various hematological malignancies and currently being evaluated in solid cancers in early phase studies. We did a systematic review consisting of 15 prospective clinical trials (n=159) evaluating CAR-T cells in solid cancers. Early phase trials showed promising response rates in ovarian epithelial cancer (100%), human epidermal growth factor receptor 2 (HER2)-positive sarcoma (67%), epidermal growth factor receptor (EGFR)-positive biliary tract cancer (65%), advanced gastric/pancreatic cancer (82%), hepatocellular carcinoma (67%), and colorectal cancer (70%). The median overall response across all malignancies was 62% (range 17%-100%). Median progression-free survival and overall survival were not reached in most trials. Cytokine release syndrome was seen in only one patient with cholangiocarcinoma who received EGFR-specific CAR-T cell therapy. Although survival data is still not mature, CAR-T cell therapy in solid malignancies did show encouraging response rates and was well-tolerated.

Effects of Essential Fatty Acid Supplementation on in vitro Fermentation Indices, Greenhouse Gas, Microbes, and Fatty Acid Profiles in the Rumen.

This study estimated the effect of essential fatty acid (FA) supplementation on fermentation indices, greenhouse gases, microbes, and FA profiles in the rumen. The treatments used pure FAs consisting of C18:2n-6 FA (LA), C18:3n-3 FA (LNA), or a mixture of these FAs at 1:1 ratio (Combo). In vitro rumen incubation was performed in 50 mL glass serum bottles containing 2 mg of pure FAs, 15 mL of rumen buffer (rumen fluid+anaerobe culture medium = 1:2), and 150 mg of synthetic diet (411 g cellulose, 411 g starch, and 178 g casein/kg dry matter) at 39°C for 8 h with five replications and three blanks. In rumen fermentation indices, LA exhibited highest (P < 0.05) ammonia-N and total gas volume after 8 h of incubation. Furthermore, LA presented lower (P < 0.05) pH with higher (P < 0.05) total volatile fatty acid (P = 0.034) than Combo, while LNA was not different compared with those in the other treatments. Additionally, Combo produced highest (P < 0.05) CO2 with lowest (P < 0.05) CH4. In the early hours of incubation, LA improved (P < 0.005) Fibrobacter succinogenes and Ruminococcus flavefaciens, while LNA improved (P < 0.005) Ruminococcus albus. After 8 h of incubation, LNA had lower (P < 0.05) methanogenic archaea than LA and Combo but had higher (P < 0.05) rumen ciliates than LA. R. albus was higher (P < 0.05) in LA than in LNA and Combo. It was observed that the rate of biohydrogenation of n-6 and n-3 FAs was comparatively lowest (P < 0.05) in Combo, characterized by higher C18:2n-6 and/or C18:3n-3 FA and polyunsaturated FA (PUFA) concentrations with lower (P < 0.05) concentrations of C18:0 and saturated FA and the ratio of saturated FAs to PUFAs. Therefore, this study concluded that dietary C18:2n-6 could improve populations of fibrolytic bacteria and rumen fermentation indices, but dietary mixture of pure C18:2n-6 and C18:3n-3 is recommended because it is effective in reducing enteric methane emissions and resisting biohydrogenation in the rumen with less effect on rumen microbes.

Rare monosomy 7 and deletion 7p at diagnosis of chronic myeloid leukemia in accelerated phase.

Clonal cytogenic evolution with the development of additional chromosomal abnormalities (ACAs) in chronic myelogenous leukemia (CML) is a marker for disease progression and is known to impact therapy and survival. The presence of ACAs has been shown to affect the responses to tyrosine kinase inhibitors (TKI) in patients with newly diagnosed CML in accelerated phase (CML-AP). We report a rare case of a CML patient who presented in CML-AP and was found to have multiple ACAs including monosomy 7, deletion 7p, trisomy 8, and an extra Philadelphia chromosome (Ph) in separate Ph-positive cell line, respectively. Six months after combined chemotherapy with TKI, the patient achieved a major cytogenetic response with disappearance of monosomy 7/deletion 7p with no major molecular response.

Biliary cancer: gateway to comprehensive molecular profiling.

Cholangiocarcinoma is a rare malignancy with a poor prognosis. The majority of tumors present at an advanced stage, and relapse often occurs after surgery conducted with curative intent. In both of these cases, standard treatment is a combination of cisplatin and gemcitabine. The use of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) in second-line treatment improves survival, but outcomes remain dismal. Studies have shown that cholangiocarcinoma possesses a wide spectrum of genetic aberrations. Clinical trials evaluating targeted therapies in patients with FGFR2 fusions, IDH1 mutations, and BRAF mutations have yielded very promising results, and the agents were generally well tolerated. Several FGFR2 fusion-targeted agents have achieved response rates between 20.7% and 35.5%, with disease stability rates ranging between 76% and 82%. Agents targeting FGFR2 fusions also have produced median progression-free survival (PFS) ranging from 5.7 to 6.9 months and median overall survival (OS) ranging from 12.5 to 21.1 months. Ivosidenib in patients with an IDH1/2 mutation has produced a response rate of 2% and a disease stability rate of 51%, with median PFS of 2.7 months and median OS of 10.8 months. In patients with a BRAF mutation, a combination of dabrafenib and trametinib led to an overall response rate of 51% and disease stability in another 40% of patients. Median PFS and OS were 9 and 14 months, respectively. Patients should be encouraged to participate in clinical trials.

The Perspective of a Breast Cancer Patient: A Survey Study Assessing Needs and Expectations.

Background Patient satisfaction is one of the key indicators of health care quality. We aim to identify patient's needs and expectations in a breast cancer clinic to provide patient-centered care and better overall satisfaction.  Methods A 17-item survey was administered to 110 patients at a breast cancer clinic. The survey was designed after a thorough literature review and approved by an oncologist and a palliative care physician.  Results Self-reported knowledge about the disease was reported adequate by 90.9% of our patients yet only 55.45% of our patients could identify the stage of their cancer. More education was desired by 32.7% of patients including various treatment options (29%), common complications (24.5%), prognosis (26.3%) and risk factors (11.8%). The majority of our patients were having some form of cancer-related emotional stress and physical symptoms. The majority of our patients (57.27%) wanted their oncologist to address social/emotional issues and 25.45% felt the need for more focus on physical symptoms in their subsequent visits. End-of-life (EoL) care discussions were considered an integral component of overall care by 29% of our patients. Components of EoL care discussions that patients stated they could benefit from included prognosis (27.27%), life expectancy (29%), the treatment effect on the quality of life (22.7%), palliative care (9%), hospice (10.9%), advance directives (11.8%), and family involvement in medical decision-making (13.6%). There was a difference noted regarding their EoL care discussion based on the stage of cancer. Patients with early-stage disease wanted their oncologists to decide on the frequency of this discussion (72.7%). Patients with advanced disease wanted EoL care discussion to be done more frequently as initiated by them or their oncologist or if there's a change in the treatment plan.  Conclusions A discrepancy between self-reported and actual knowledge in breast cancer patients emphasizes the need for patient education. Most patients rely on their oncologists for their diagnosis-related emotional and social issues. Surprisingly, more than a quarter of our patients consider EoL care discussions important even though the majority of our patients were healthy and having stage I and II disease.

Progressive left lower extremity weakness in a patient with multiple myeloma: A diagnostic dilemma.

Extramedullary plasmacytoma is a type of plasma cell dyscrasia that can present as solitary tumor or secondary to multiple myeloma. We experienced a case of intramuscular plasmacytoma in the left thigh muscles of a patient secondary to multiple myeloma. A 73-year-old male with relapsed multiple myeloma and bilateral hip arthroplasty complained of lxeft lower limb weakness and hip pain 3 months after relapse. He underwent contrast-enhanced magnetic resonance imaging of lumbar spine and hip which was inconclusive. Subsequently, patient had multiple admissions for progressive lower limb weakness. His clinical course was complicated by a biopsy-proven plasmacytoma of the neck. He received localized radiation therapy to the neck in addition to a change in multiple myeloma chemotherapy regimen, resulting in resolution of the neck mass but his left lower extremity weakness continued to worsen. Repeat magnetic resonance imaging of hip and spine revealed an intramuscular mass in left thigh which was consistent with the diagnosis of extramedullary plasmacytoma on biopsy. Localized radiation to the thigh accompanied with a change in chemotherapy improved his symptoms and a significant reduction in size of plasmacytoma was observed. When an unexplained lower limb weakness is encountered with a history of multiple myeloma, secondary intramuscular plasmacytoma should be considered.

Desensitization therapy using 'Mariana Castells' protocol in a patient with multiple autoimmune disorders- does it work?

Clinical use of antibiotics is becoming more widespread with each passing day for various infectious diseases. This has caused an abrupt increase in hypersensitivity reactions linked to these drugs, sometimes preventing the use of first-line therapies. In these patients, clinical presentation may vary from mild skin infections to life-threatening anaphylactic reactions. Our patient is a 30 year old female with past medical history significant for mast cell activation syndrome and multiple autoimmune diseases who presented with chief complaint of fever. Patient was diagnosed with MSSA bacteremia requiring the start of an antibiotic regimen. Mariana castells protocol was used for desensitizing the patient before starting her on antibiotic regimen. Patient was desensitized in 2 days using the standard 12-step protocol and started on cefazolin for her long-term treatment of the infection. No acute episodes of drug hypersensitivity were reported. During the course of her hospital admission, she improved significantly with no complications. Our patient having a history of both multiple autoimmune diseases and mast-cell activation syndrome tolerated the protocol well with no complications. Appropriate treatment of the reactions including epinephrine use and management with personalized desensitization protocols can enhance the quality of life, life expectancy, and safety of an increasing at risk population of patients with infectious diseases allergic to their best medications. Protocols, such as mariana castells, are completely safe in autoimmune disorders and should be utilized as the standard of care in appropriate patient population.

Efficacy of Ibrutinib-Based Regimen in Chronic Lymphocytic Leukemia: A Systematic Review.

Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.

Spindle Cell Carcinoma of the Lung/Pleura: An Incidental Finding.

A 59-year-old male with a medical history of abdominal aortic dissection underwent a follow-up computed tomography (CT) scan abdomen, which showed an incidental pleural-based mass in the left lung base. The patient underwent an ultrasound (US)-guided biopsy and the histology was consistent with spindle cell carcinoma (SpCC). Staging workup was concerning for a metastatic lesion on the adrenal gland. The patient refused surgery and was subsequently started on chemotherapy. SpCC is a rare histological variant of sarcomatoid carcinoma. The prognosis is generally poor and treatment is the same as for other non-small cell lung cancers (NSCLC). The literature on disease progression and treatment is limited.

Improving Blood Transfusion Practices in a Community Hospital Setting: Our Experience with Real-Time Clinical Decision Support.

There is good evidence that 50% or more of red blood cell (RBC) transfusions are unnecessary. To curtail inappropriate RBC transfusions at our hospital, real-time clinical decision support was implemented in our electronic medical record (EMR) that alerts clinicians to the patient's most recent pretransfusion hemoglobin value upon order entry and provides Best Practice Advisory. This is a soft pop-up alert which is activated when the hemoglobin exceeds 7 g/dL. The ordering clinician can either honor (by cancelling the order) or override the alert. We studied the impact of the alert on blood utilization during a 3-month period (November 2016 to January 2017). For patients who were transfused despite the alert, a retrospective review of the medical chart was performed to determine whether or not the transfusion was clinically indicated. During the study period, 178 of the 895 RBC transfusion orders (20%) triggered the alert. After excluding duplicates, 144 orders were included in our analysis. Most of these orders (124/144, 86%) were carried out despite the alert. According to our chart review, 48% of the alert transfusions could be considered inappropriate, with hemodynamically stable, asymptomatic anemia being the leading indication. Of clinical services, orthopedic surgery had the highest rate of overriding the alert with no clinical justification (70%). The number of RBC transfusions dropped from 313.5 units per month (preintervention period) to 293.2 units per month (postintervention period)-a 6.5% decrease. Real-time clinical decision support may reduce the number of inappropriate RBC transfusions in a community hospital setting, though in our study, the decrease in blood utilization (6.5%) did not reach statistical significance.

Possible Predictive Factors for In-hospital Cardiac Arrest in Patients with Cancer: A Retrospective Single Center Study.

BACKGROUND: Despite cancer being the second most common cause of death in the United States, more people are living longer after the diagnosis of cancer than before. Healthcare workers will be treating an increasing number of patients with cancer. Various studies have identified predictors of cardiac arrest in the general population, however, none have been done to identify such factors in cancer patients who form a more vulnerable group with lower survival rate following cardiac arrest. METHODS: We retrospectively analysed charts of all patients with active cancer who experienced in-hospital cardiac arrest (IHCA) and underwent cardio-pulmonary resuscitation (CPR) from January 2015 to December 2017 at our hospital (n=44, group A). We compared this group to 44 consecutive patients with active cancer admitted to the oncology unit who did not experience cardiac arrest (n=44, group B). We excluded patients in remission. RESULTS: Both the groups were comparable in terms of age (69 ± 14 vs 68 ± 15, p=0.776) and gender distribution (50% vs 56% males, p=0.521). Prevalence of coronary artery disease (CAD) (25% vs 11%, p=0.097), hypertension (68% vs 66%, p=0.821), hyperlipidaemia (34% in both groups, p=1.000), tobacco abuse (18% vs 27%, p=0.308), and diabetes mellitus (34% vs 23%, p=0.237) was not significantly different between the two groups. Group with cardiac arrest had significantly higher alanine aminotransferase (100 U/L ± 150 vs 47 U/L ± 87, p=0.043), alkaline phosphatase (288 U/L ± 512 vs 118 U/L ± 80, p=0.032), creatinine (1.8 mg/dl ± 1.74 vs 1.1 mg/dl ± 0.76, p=0.023), international normalised ratio (INR) (2.1 ± 1.5 vs 1.2 ± 0.5, p=0.005), and lower estimated -glomerular filtration rate (43 mL/min/1.73m2 ± 17 vs 51 mL/min/1.73m2 ± 15, p=0.022) on admission. Group A also had significantly higher incidence of sepsis during the hospital course as compared to group B (30% vs 2%, p<0.001). In group A, 11.4% survived to discharge as compared to 95.5% in group B. Significantly higher number of patients in group B were taking chemotherapy (77.27% vs 34.09%, p=0.000046) and radiation therapy (65.9% vs 22.72%, p=0.000046) as compared to group A. CONCLUSION: Cancer patients who experienced IHCA had worse renal and hepatic function; they were frequently diagnosed with sepsis and had similar cardiovascular risk factors as compared to cancer patients who did not experience cardiac arrest. Furthermore, a higher number of patients with active cancer who did not experience cardiac arrest were on chemotherapy, immunotherapy or radiation therapy.