Administration of solid oral drug products via enteral feeding tubes (EFTs) is common due to the lack of suitable alternatives but is associated with substantial risk of drug loss. A novel in vitro setup was developed to simulate clinical administration, considering patient supine positioning, tube temperature control, tube diameter and material, and nutritional formula supply. Drug recovery of furosemide and levothyroxine was evaluated under best- and worst-case administration conditions over several days. Under best case conditions, including multiple syringe and tube flushing steps, recovery exceeded 90 percent for both drugs. Under worst-case conditions, where flushing was omitted, furosemide recovery on day one reached approximately 90 percent in 14 French tubes and 70 percent in 10 French tubes, while levothyroxine recovery was around 80 percent across all tubes. Drug recovery in 14 French tubes declined over time, reflecting sedimentation, incomplete syringe emptying, and interactions with nutritional formula. During nutritional supply, agglutination of nutrient formula and increased back pressure occurred, and residual deposits and bacterial colonization were observed at the tube interior. These findings underscore the critical role of flushing syringes and EFTs to maximize dose recovery and prevent tube obstruction. The study demonstrates that clinically relevant administration factors including tube diameter, duration of nutrition, and procedural adherence substantially influence delivered drug doses. The presented in vitro model provides a standardized, practice-oriented platform for evaluating drug recovery through EFTs, supporting optimization of clinical administration protocols and guiding future recommendations.

Phototransformation is an important attenuation process for pharmaceuticals in the aquatic environment. However, there are unknowns regarding the kinetics, products, and mechanisms of the sensitized photolysis of many pharmaceuticals induced by natural sensitizers. In this study, we systematically investigated the photochemical behavior and fate of the diuretic furosemide (FUR) under natural sunlight in the presence of nitrate (NO3[-]) and dissolved organic matter (DOM). Results show that NO3[-] significantly promoted the photodegradation of FUR through photosensitization, with photolysis rate constant in the presence of 1 mM NO3[-] being approximately 1.6-fold higher than that of direct photolysis. The photolysis of FUR predominantly generated hydroxylated product, whose generation and degradation were both facilitated by NO3[-]. DOM exhibited inhibitory effects on NO3[-]-sensitized photolysis of FUR by light screening and radical quenching. The photolysis pathways of FUR in the presence of NO3[-] included decarboxylation, C-N bond cleavage, dechlorination, hydroxylation, ring opening, dehydrogenation, and desulfonamidation. Most photoproducts were predicted to be less ecotoxic, persistent, and bioaccumulative than FUR. Model predictions with APEX indicate that direct photolysis and reaction with carbonate radical were the primary photochemical processes for FUR dissipation in natural waters. The photolysis half-lives of FUR were significantly affected by dissolved organic carbon and water depth. Results of this study fulfill the knowledge gaps in the photochemical behavior and fate of the diuretic drugs in sunlit surface waters.

A 14-year-old domestic shorthair cat was examined because of respiratory distress. Thoracic radiography showed a prominent aortic arch and no other abnormalities. Echocardiography documented a mobile flap within the ascending aorta creating 2 lumens, consistent with aortic dissection (AD), mild pericardial effusion with tamponade, left ventricular concentric hypertrophy, and normal left atrial size. Systemic hypertension (200 mmHg) was the presumed cause of AD, prompting administration of telmisartan, furosemide, and amlodipine. The cat clinically improved, became normotensive, and was discharged 2 days later. The cat remained well for 4 months, then became lethargic and died. Necropsy showed a 7.6 cm long aortic intimal flap, severe bacterial aortic endarteritis, and evidence of sepsis including multiple organ necrosis, thrombosis, and embolic glomerulonephritis. Bacterial culture of the kidneys yielded mixed bacterial growth including Pasteurella stomatis, presumably the same bacterium identified in the endarteritis lesion. Infective aortic endarteritis can be a fatal complication of AD.

A 14-month-old, male castrated, 3,9-kg Singapura cat was referred for treatment of severe pulmonary valve stenosis associated with tricuspid valve dysplasia. The cat was pretreated with atenolol and scheduled for pulmonary balloon valvuloplasty. Because the right femoral vein could not accommodate a 5 Fr introducer, vascular access was obtained via the left external jugular vein, followed by right ventricular catheterisation, pressure measurement and angiography. A 10 mm low pressure balloon catheter was advanced over a guidewire to the level of the pulmonary valve and inflated once, resulting in complete loss of the balloon waist. During the procedure, the cat was severely hypotensive for 30 minutes, lasting from the time of ca-theterisation of the right ventricular outflow tract until nearly the end of anaesthesia. Postoperative tachypnoea was attributed to congestive heart failure, although aspiration pneumonia could not be excluded. The patient was discharged the day after the intervention following a single dose of furosemide and received amoxicillin-clavulanate for ten days. Echocardiography after eleven days, three months and 16 months demonstrated a marked and sustained reduction of the transvalvular pressure gradient. The cat showed an improved activity level after the procedure, which persisted over the 16-month follow-up period.

Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of morbidity, mortality, and healthcare burden. While standard bronchodilator therapy alleviates airway obstruction, its efficacy is often limited. This study evaluated nebulized furosemide, which has bronchodilatory and anti-inflammatory effects, as an adjunct to salbutamol-ipratropium in hospitalized COPD patients. Ninety‑two patients with exacerbated COPD were randomly assigned to two equal groups (46 each). The intervention group received nebulized salbutamol-ipratropium plus furosemide (20 mg), and the control group received salbutamol-ipratropium, both every 8 hours for 10 minutes over 5 consecutive days. Demographic and clinical variables, pulmonary function indices (FEV1, FVC, FEV1/FVC), clinical outcomes (COPD Assessment Test (CAT), Modified Medical Research Council (mMRC)scores, and quality of life by St. George's Respiratory Questionnaire (SGRQ)), arterial blood gases, and inflammatory biomarkers (TNF-α, IL-6, IL-8, CRP, ESR, neutrophil %, WBC) were measured before and after treatment. Demographic characteristics and baseline indices did not differ significantly between the groups. Dyspnea and respiratory symptoms (mMRC and CAT scores) decreased significantly, while quality of life, improved markedly in the intervention group compared to the control group. Pulmonary function also showed significant enhancement, with the FEV1/FVC ratio increasing. Arterial blood gas analysis showed higher PaO2 and lower PaCO2 in the intervention group. IL-6 and IL-8 decreased significantly, and no adverse events were reported. Nebulized furosemide enhances standard therapy in COPD exacerbations, improving lung function, relieving symptoms, and reducing systemic inflammation. Its safety, accessibility, and low cost make it a promising adjunct treatment.

Fruquintinib (FRU) is a vascular endothelial growth factor receptor (VEGFR)-1, 2, 3 tyrosine kinase inhibitor (TKI) approved for metastatic colorectal cancer. While hypertension, fatigue, and hand-foot syndrome are common adverse events, severe proteinuria and nephrotic syndrome are rare and has not been reported in clinical trials. A woman in her 60s with recurrent rectal cancer began fruquintinib at 5 mg/d as a 4th-line treatment. She had a history of hypertension and was taking amlodipine. On day 8 of the first cycle, she developed hypertension (grade 2) . On day 22, proteinuria (grade 3) was detected and hypertension had worsened (grade 3) . Since these changes occurred during the off-treatment period, observation was selected. However, on day 23, the patient presented with fatigue, generalized edema, and dyspnea. Laboratory tests revealed a urine protein/creatinine ratio of 10.3 g/gCr and elevated serum creatinine (grade 1), leading to hospitalization. Post-admission, hypermagnesemia (grade 3) was also noted. loxoprofen and magnesium oxide were discontinued and furosemide was initiated. By day 6 of hospitalization, 24-h urine protein quantification had decreased to 2.1 g/d. By day 9, edema and hypertension had both improved, and the patient was discharged. The Naranjo score were 7 for fruquintinib, 6 for loxoprofen and bevacizumab, and 5 for trifluridine/tipiracil hydrochloride, suggesting probable adverse drug reaction. VEGFR-TKIs are presumed to impair glomerular structure and function, leading to proteinuria. Although renal biopsy was not performed, thrombocytopenia and elevated lactate dehydrogenase suggested thrombotic microangiopathy. Earlier monitoring could have enabled faster detection and prevention of severe symptoms.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia causes substantial morbidity, but tissue reservoirs that permit bacterial persistence remain poorly defined. Using intravenous USA300 MRSA infection in mice, multiplexed imaging, dual-species transcriptomics, host and bacterial genetics, and cell-based assays, we uncovered the renal inner medulla, the site of urine concentration, as an MRSA reservoir. In this hyperosmotic niche, MRSA evaded immune detection and co-opted tissue polyamines to sustain growth, enabling subsequent spread toward the renal cortex. Neutrophil recruitment to the inner medulla was profoundly delayed owing to osmotic inhibition of immune cell migration. Disruption of medullary osmolality with the loop diuretic furosemide accelerated neutrophil infiltration, limited bacterial spread, and improved renal outcomes. Mechanistically, polyamines promoted MRSA persistence through both extracellular and intracellular actions that depended on local osmolality and pH. In the medullary milieu, polyamines primarily associated with the bacterial surface and stabilized membranes against osmotic stress. Intracellular polyamines enhanced translation of guaB (inosine monophosphate dehydrogenase), the rate-limiting enzyme in bacterial de novo purine biosynthesis. The polyamine-catabolizing gene speG (spermidine acetyltransferase), uniquely present in epidemic USA300 MRSA strains, mitigated polyamine toxicity and conferred a selective advantage in the polyamine-rich kidney. These findings revealed the inner medulla as a physiologically immune-restricted MRSA reservoir and supported modulation of medullary osmolality and bacterial polyamine metabolism as candidate adjunctive strategies for limiting renal persistence and dissemination during MRSA bacteremia.

Hepatocellular carcinoma (HCC) remains a major challenge threatening global health. It has a high incidence with poor prognosis, and its response to current conventional therapies is not satisfactory, so we need to explore new effective therapies to address this problem. Targeted therapy represents a promising approach, but the therapeutic efficacy of targeting ion transporters and nuclear transport proteins, such as Na+/K+/2Cl- cotransporter 1 (NKCC1) and Karyopherin β1 (KPNβ1), remains poorly investigated. This study aims to assess the therapeutic efficacy of targeting NKCC1 and KPNβ1 individually and in combination. We also explored the roles of these transporters in tumor cell proliferation and HCC progression. To achieve this aim, an HCC rat model was used, induced by diethylnitrosamine and phenobarbital. The evaluation included histopathological examination and assessment of liver function biomarkers (alanine aminotransferase and aspartate aminotransferase), cell cycle regulators (Cyclin D1, p21, E2F1), proliferation (Ki-67), apoptosis (Caspase-3), and expression of NKCC1 and KPNβ1. This study revealed that NKCC1 and KPNβ1 were upregulated in the HCC group. This increase was associated with increased proliferation and suppressed apoptosis. Targeting these proteins, particularly in combination, significantly improved liver function. It also induced cell cycle arrest, reduced proliferative markers, and enhanced apoptosis. These findings indicate that NKCC1 and KPNβ1 could serve as possible therapeutic targets in HCC treatment.

Severe hyponatremia is uncommon in pregnancy but has been described in association with preeclampsia, particularly in severe disease and multifetal gestation. We report a 38-year-old gravida 1 para 0 with dichorionic-diamniotic twins who presented at 29 weeks and four days of gestation and developed rapidly progressive hypotonic hyponatremia, with serum sodium decreasing from 126 to 110 mmol/L. Low serum osmolality with inappropriately concentrated urine, elevated urine sodium, normal thyroid testing, preserved renal function, and the initial clinical volume assessment supported a pattern consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH); however, cortisol was not obtained during the hospitalization, so adrenal insufficiency was not completely excluded biochemically. Fluid restriction, hypertonic saline, and furosemide were limited by pulmonary edema, and persistent severe hyponatremia prompted multidisciplinary use of tolvaptan despite limited pregnancy safety data. Cesarean delivery was subsequently performed in the setting of worsening maternal disease. Maternal serum sodium normalized postpartum without documented neurologic complications, supporting a pregnancy-mediated disturbance of water balance. This case highlights the diagnostic overlap between preeclampsia-associated hyponatremia and SIADH, the narrow therapeutic margin created by pulmonary edema, and the importance of close sodium monitoring and timely delivery when maternal status deteriorates.

ObjectiveAt the end of life, changing healthcare needs may lead to decreased use of preventive therapies and increased use of medications for symptom management. This study compared polypharmacy, hyperpolypharmacy, and medication-dispensing patterns among community-dwelling older adults with dementia, community-dwelling older adults without dementia, and older adults with dementia in long-term care.MethodsWe completed a retrospective, matched case-control study using linked administrative health data from Nova Scotia, Canada. We compared polypharmacy, hyperpolypharmacy, and medications dispensed among three groups (community-dwelling older adults with dementia, community-dwelling older adults without dementia, and older adults with dementia in long-term care). We chose community-dwelling older adults with dementia with dates of death between 1 January 2019 and 1 January 2021, and then matched with replacement to community-dwelling older adults without dementia and older adults with dementia in long-term care based on age, administrative sex, and date of death ±30 days. Descriptive comparisons of polypharmacy, hyperpolypharmacy, and medications used during each of three equal periods of the last year of life (early, mid, and late) were made. Logistic regression was used to estimate the probability of polypharmacy and hyperpolypharmacy, adjusting for demographic and clinical factors.ResultsEach group included 1274 individuals. The mean age was 84.8 years. Overall, 50.9% (1944/3822) experienced polypharmacy and 8.7% (332/3822) hyperpolypharmacy, with community-dwelling older adults with dementia consistently having the highest rates. The most common medications dispensed in the last year of life were furosemide, levothyroxine sodium, salbutamol, and vitamin B12.ConclusionsCommunity-dwelling older adults with dementia had the highest rates of polypharmacy and hyperpolypharmacy across all time periods assessed. Medications most frequently dispensed in the last year of life did not change in ways that would be expected if deprescribing recommendations were being followed. This suggests that prescribing and deprescribing at the end of life are potential areas for pharmacist support and involvement.