Liver transplant (LT) is the treatment of choice for unresectable, localized hepatocellular carcinoma (HCC). However, transplant is not recommended for patients who have extensive tumor growth and do not meet specific criteria. For these cases, \"bridging\" therapies are often used to either downstage or prevent tumor progression while patients are on the transplant list. Various pre-transplant therapies have been used, including transarterial chemoembolization, radiofrequency ablation, and systemic therapies. Sorafenib is a well-known systemic agent used for HCC, but research is limited on its use as well as the use of newer agents as bridging therapy. Prospective studies are also lacking. We discuss cases of two patients diagnosed with HCC and treated systemically with cabozantinib prior to transplant without treatment-related complications. This suggests that cabozantinib could be safely used after sorafenib therapy to control disease related to HCC while awaiting liver transplantation.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has gained renewed interest as a bridge to transcatheter aortic valve replacement (TAVR) for patients with aortic stenosis (AS). However, it is unclear whether they patients should undergo TAVR directly or receive a staged bridge to BAV before TAVR is unclear. We used a national database to examine the association between BAV and TAVR in patients with TAVR and its effect on in-hospital mortality.
METHODS: Using the nationwide inpatient database of the Japanese registry of all cardiac and vascular diseases and the combination of the diagnosis procedure combination, we retrospectively analyzed 27,600 patients with AS who underwent TAVR between October 2013 and March 2021. Outcomes of the direct TAVR group (n = 27,387) were compared with those of the BAV bridge to TAVR group (n = 213), which received BAV at least 1 day before TAVR.
RESULTS: The median age was 85 (interquartile range: 82-88) years, with 33.3% (n = 9188) being male. Unplanned/emergent admissions increased with TAVR, whereas the use of BAV bridge to TAVR decreased. The in-hospital mortality rate was 1.3% and decreased over time. However, the BAV bridge to TAVR had a significantly higher in-hospital mortality than direct TAVR (5.6% vs. 1.3%; p < .0001). Factors associated with in-hospital mortality included age, body mass index, chronic renal disease, percutaneous coronary intervention, and BAV bridge to TAVR.
CONCLUSIONS: In unplanned/emergent and planned admission settings, the in-hospital mortality rate for BAV bridge to TAVR is worse than that for direct TAVR. Practical criteria for BAV bridge to TAVR should be proposed to improve outcomes.

Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.

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Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy. However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells. This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide. We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors. Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes. In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.

Cases that are inoperable owing to poor preoperative conditions are sometimes encountered. However, there are some cases that are led to radical treatment by performing bridge therapy. Here, we presented a case of a patient with complex cardiac disease in an inoperable state who underwent bridging therapy that led to successful surgical treatment. A 73-year-old male who received hemodialysis treatment and had severe aortic valve stenosis and coronary artery disease planned surgical treatment. However, he was deemed inoperable owing to his low cardiac function and hemodynamic instability. Therefore, to escape from a fatal condition, we first performed balloon aortic valvuloplasty and percutaneous coronary intervention as palliative procedures. Subsequently, his cardiac function and hemodynamic stability remarkably improved; therefore, after 1 month, we performed a successful radical surgical treatment. Even in inoperable patients, bridging therapy leading to radical treatment is possible.

OBJECTIVE: The aim of this study was to investigate the efficacy of percutaneous cholecystostomy (PC) in the geriatric patients with acute cholecystitis.
METHODS: The records of geriatric patients with high surgical risk who underwent percutaneous cholecystostomy for acute cholecystitis were reviewed retrospectively.
RESULTS: The median age of 134 patients who underwent percutaneous cholecystostomy was 77 (65-98) years and 63.4% were women. The mean length of hospital stay was 5 (4-18) days, and the follow-up period until the procedure was 2 (1-6) days. Murphy\'s sign was positive in 79.1% of patients on physical examination, and the remaining patients (20.9%) had only tenderness on examination. As USG findings, 59.0% of the patients had a gall bladder wall thickness (> 4 mm) with pericholecystic fluid. Additional imaging method, abdominal CT, was performed in 29 patients (21.6%), MRCP was performed in three patients (2.2%), and ERCP was performed in one patient (0.7%). Bacterial growth was detected in 27.6% of the bile cultures performed. During the follow-up period, laparoscopic cholecystectomy was performed in 60.4% of the patients and open cholecystectomy was performed in 5.2% of the patients electively. 34.3% of the patients did not undergo any surgery. Bile leakage was detected in two patients (1.5%) as a procedure-related complication, and no mortality was observed.
CONCLUSIONS: Abdominal ultrasonography-guided PC is a safe and effective method in the management of acute cholecystitis in high-risk patients in the geriatric age group.

BACKGROUND: Fosfomycin acts against aerobic Gram-/+ bacteria by blocking the synthesis of peptidoglycan. Its use has been currently re-evaluated for intravenous administration for the treatment of systemic infections by multidrug-resistant bacteria. Concentration-/time-dependent activity has been suggested, with potential clinical advantages from prolonged or continuous infusion. Nevertheless, little is known about Fosfomycin stability in elastomeric pumps. The aim of the present work was stability investigation before administration at 4 °C and during administration at 34 °C.
METHODS: InfectoFos® (InfectoPharm s.r.l., Milan, Italy) preparation for intravenous use in elastomeric pumps at 4 °C and 34 °C was analyzed following EMA guidelines for drug stability. Samples were analyzed with an ultra-high performance liquid chromatography coupled with tandem mass spectrometry method on a LX50® UHPLC system equipped with a QSight 220® (Perkin Elmer, Milan, Italy) tandem mass spectrometer.
RESULTS: Fosfomycin in elastomeric preparation is stable for at least 5 days at a storage temperature of 4 °C and 34 °C.
CONCLUSIONS: The results suggest Fosfomycin eligibility for continuous infusion even in the context of outpatient parenteral antibiotic therapy. Therefore, this approach should be tested in clinical and pharmacokinetic studies, in order to evaluate the possible gains in the pharmacokinetic profile and the clinical effectiveness.

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Aim: To assess bridging glatiramer acetate (GA) or IFN-β for relapse prevention in women with relapsing multiple sclerosis planning pregnancy. Materials & methods: Participants discontinued disease-modifying therapies (DMTs) and received GA/IFN (early- or delayed-start) or no DMT (control) until pregnancy. Results: Annualized relapse rate was lower in delayed-start GA/IFN cohort versus control during washout/bridging. During washout/bridging, bridging with GA/IFN in this cohort reduced clinical activity, while disease activity increased in controls versus baseline. Conclusion: More data on GA/IFN bridging are needed. Women with low relapsing multiple sclerosis activity in the year prior to DMT discontinuation due to pregnancy planning benefited from GA/IFN bridging with lower annualized relapse rate versus no treatment and reduced clinical activity versus baseline during washout/bridging and pregnancy.
When women with relapsing multiple sclerosis (RMS) plan a pregnancy, doctors must think about the possible effects of medicines. Patients can take medicines with a well-defined safety profile to reduce the risk of attacks after stopping strong treatments. In this study, women stopped taking their RMS medicines and either: took well-defined RMS medicines, glatiramer acetate (GA) or IFN-β; or stopped all RMS medicines. The rate of attacks (in a year) was lower in patients who started taking GA/IFN a while after stopping their previous RMS medicines compared with patients who took no more medication. Women with low RMS activity in the year before stopping RMS treatment because of pregnancy planning may benefit from GA/IFN treatment prior to conception.