Routine invasive strategy and frailty burden in non-ST-segment elevation acute myocardial infarction

Objective To assess the prognostic impact of a routine invasive strategy according to the frailty burden in patients with non-ST-segment elevation myocardial infarction(NSTEMI)from the MOSCA-FRAIL clinical trial.Methods The MOSCA-FRAIL trial randomized 167 frail patients,defined by a Clinical Frailty Scale(CFS)≥4,with NSTEMI to an invasive or conservative strategy.The primary endpoint was the number of days alive and out of hospital(DAOH)one year after discharge.For this subanalysis,we compared the impact of an invasive strategy on the outcomes between vulnerable(CFS=4,n=43)and frail(CFS>4,n=124)patients.Results Compared to vulnerable patients,frail patients presented lower values of DAOH(289.8 vs.320.6,P=0.146),more read-missions(1.03 vs.0.58,P=0.046)and higher number of days spent at the hospital during the first year(10.8 vs.3.8,P=0.014).The cau-ses of readmission were mostly non-cardiac(56%).Among vulnerable patients,DAOH were similar regardless of strategy(invasive vs.conservative:325.7 vs.314.7,P=0.684).Among frailest patients,the invasive group tended to have less DAOH(267.7 vs.311.1,P=0.117).Indeed,patients with CFS>4,invasively managed lived 29 days less than their conservative counterparts.In contrast,the-re were no differences in the subgroup with CFS=4.Conclusions Adult patients with frailty and NSTEMI showed different prognosis according to the degree of frailty.A routine in-vasive strategy does not improve outcomes and might be harmful to the frailest patients.

Endoscopic ultrasound guided vascular access and therapy:A promising indication

Endoscopic ultrasound(EUS)is an imaging technique that has consolidated its role as an important tool for diagnosis and therapeutics.In recent years we have seen a dramatic increase in the number of EUS-guided therapeutic indications(celiac plexus neurolysis/block, pseudocyst drainage,etc).Preliminary reports have suggested EUS may also be used to guide vascular access for both imaging and treating different vascular diseases.This review aims to objectively describe the existing evidence in the field.

Small renal masses in kidney transplantation:Overview of clinical impact and management in donors and recipients

Kidney transplantation is the best replacement treatment for the end-stage renal disease.Currently,the imbalance between the number of patients on a transplant list and the number of organs available constitutes the crucial limitation of this approach.To expand the pool of organs amenable for transplantation,kidneys coming from older patients have been employed;however,the combination of these organs in conjunction with the chronic use of immunosuppressive therapy increases the risk of incidence of graft small renal tumors.This narrative review aims to provide the state of the art on the clinical impact and management of incidentally diagnosed small renal tumors in either donors or recipients.According to the most updated evidence,the use of grafts with a small renal mass,after bench table tumor excision,may be considered a safe option for high-risk patients in hemodialysis.On the other hand,an early small renal mass finding on periodic ultrasound-evaluation in the graft should allow to perform a conservative treatment in order to preserve renal function.Finally,in case of a renal tumor in native kidney,a radical nephrectomy is usually recommended.

GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Non-small cell lung cancer(NSCLC) is a heterogeneous disease accounting for approximately 85% of all lung cancers. Only 17% of patients are diagnosed at an early stage. Treatment is multidisciplinary and radiotherapy plays a key role in all stages of the disease. More than 50% of patients with NSCLC are treated with radiotherapy(curative-intent or palliative). Technological advancesincluding highly conformal radiotherapy techniques, new immobilization and respiratory control systems, and precision image verification systems-allow clinicians to individualize treatment to maximize tumor control while minimizing treatment-related toxicity. Novel therapeutic regimens such as moderate hypofractionation and advanced techniques such as stereotactic body radiotherapy(SBRT) have reduced the number of radiotherapy sessions. The integration of SBRT into routine clinical practice has radically altered treatment of early-stage disease. SBRT also plays an increasingly important role in oligometastatic disease. The aim of the present guidelines is to review the role of radiotherapy in the treatment of localized, locally-advanced, and metastatic NSCLC. We review the main radiotherapy techniques and clarify the role of radiotherapy in routine clinical practice. These guidelines are based on the best available evidence. The level and grade of evidence supporting each recommendation is provided.

CONJUNCTIVAL IMPRESSION CYTOLOGY AFTER GLAUCOMA FILTERING SURGERY

Purpose: To evaluate the postoperative ocular surface modifications by conjunctival impression cytology after filtering surgery. Methods: We have prospectively studied 27 eyes of 23 patients who underwent trabeculectomy or non-penetrating deep sclerec-tomy. Conjunctival impression cytology was performed before surgery and 15 days, 1,3 and 6 months after filtering surgery. We evaluated the degree of squamous metaplasia and the

TOPOGRAPHIC CONCORDANCE BETWEEN SHORT WAVE AUTOMATED PEREMETRY AND FREQUENCY DOUBLING TECHNOLO-GY IN OCULAR HYPERTENSION

Purpose: To evaluate the topographic concordance between sensibility values of short wave automated perimetry (SWAP) and frequency doubling technology (FDT) in ocular hypertension. Methods: 22 eyes of 22 patients diagnosed of ocular hypertension underwent SWAP (24-2 test, Humphrey analyser) and FDT (C-20 threshold test). According the 17 points examined

CORRELATION BETWEEN CONVENTION-AL AUTOMATED PERIMETRY (24-2 SITA)AND FREQUENCY-DOUBLING TECHNOLO-GY IN ADVANCED GLAUCOMA

Purpose: To analyse the topographic concordance of conventional automated perimetry (24-2, SITA) and frequency doubling technology (FDT) in patients with advanced glaucoma. Methods: This prospective study included 22 consecutive patients with an advanced visual field damage in SITA (24-2) (more than 75% and less than 100% of points explored had 0 dB of threshold sensitivity). These eyes were examined with the program C-20

TOPOGRAPHICAL CHANGES AFTER PHA- COEMULSIFICATION AND DEEP SCLE- RECTOMY

Purpose: To evaluate the surgically induced corneal refraction (SICR) after phacoemulsification and deep sclerecto-my (P-DS). Methods: This prospective study included 15 eyes of 15 patients with a mean age of 32 years (range 47-90) who underwent phacoemulsification (a temporal clear cornea incision in right eye and a nasal incision in left eye), implantation of

Advanced small-bowel well-differentiated neuroendocrine tumours:An international survey of practice on 3rd-line treatment

BACKGROUND Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours(Wd-SBNETs),while and peptide receptor radionuclide therapy(PRRT)is frequently used as a second-line therapy.Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence.AIM To understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online survey.METHODS Weighted average(WA)of likelihood of usage between responders(1 very unlikely;4 very likely)was used to reflect the relevance of factors explored.RESULTS Replies from representatives of 28 centers were received(5/8/2020-21/9/2020);medical oncologist(53.6%),gastroenterologist(17.9%);United Kingdom(21.4%),Spain(17.9%),Italy(14.3%).Majority from European Neuroendocrine Tumor Society(ENETS)Centres of Excellence(57.1%),who followed ENETS guidelines(82.1%).Generally speaking,3rd-line treatment for Wd-SBNETs was:everolimus(EVE)(66.7%),PRRT(18.5%),liver embolization(LE)(7.4%)and interferon-alpha(IFN)(3.7%);chemotherapy(0%);decision was based on clinical trial data(59.3%),or personal experience(22.2%).EVE was most likely used if Ki-67<10%(WA 3.27/4)or age<70 years(WA 3.23/4),in the 3rd-line setting(WA 3.23/4);regardless of presence/absence of carcinoid syndrome(CS),rate of progression or extent of disease.Chemotherapy was mainly utilised only if rapid progression(within 6 mo)(WA 3.35/4),Ki-6710%-20%(WA 2.77/4),negative somatostatin receptor imaging(WA 2.65/4)or high tumour burden(WA 2.77/4);temozolomide or streptozocin was used with capecitabine or 5-fluorouracil(5-FU)(57.7%),FOLFOX(5-FU combined with oxaliplatin)(23.1%).LE was selected if presence of CS(WA 3.24/4)or Ki-67<10%(WA 2.8/4),after progression to other treatments(WA 2.8/4).IFN was rarely used(WA 1.3/4).CONCLUSION Everolimus was the most frequently used therapeutic option in the third-line setting.The most important factors for decision-making included Ki-67,rate of progression,functionality and tumour burden;since this decision is based on multiple factors,it highlights the need for a multidisciplinary assessment.

Response of TT virus to IFN plus ribavirin treatment in patients with chronic hepatitis C

AIM:TT virus (TTV) is a newly described DNA virus related to postransfusion hepatitis that produces persistent viremia in the absence of clinical manifestations.PEG-IFN plus ribavirin have been useful in the treatment of chronic hepatitis C infection.This study investigated the responses of TT virus (TTV) and hepatitis C virus (HCV) to PEG-IFN plus ribavirin therapy. METHODS:Fifteen patients infected with HCV were treated with PEG-IFN(0.5 μg/body weight/week) and ribavirin (1000 mg-1 200 mg/daily) for 48 weeks,Blood samples were drawn at the beginning and the end of the therapy.Serum TTV DNA and HCV RNA were quantified by real time PCR. RESULTS:At the beginning of treatment,TTV infection was detected in 10/15 (66.6%) of HCV-infected patients.Loss of serum TTV DNA at the end of therapy occurred in 6/10 (60%) patients.Out of these 6 patients,4 (67%) became positive for TTV DNA after 6 months of therapy.Regarding HCV viremia,11/15 (73%) patients were negative for serum HCV RNA after 48 weeks of therapy,7/11 (64%) of these cases also became negative for TTV DNA following the combined treatment.In the 3/4 (75%) patients who were positive for HCV RNA at the end of therapy,TTV DNA was detected as well.Sustained HCV response at 6 months after treatment was 53% (8/15). CONCLUSION:No TTV sustained response can be achieved in any patient after PEG-IFN plus ribavirin administration.

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report

BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(nab-paclitaxel)is a solvent-free taxane that has been approved for the treatment of some cancers such as breast,non-small cell lung and pancreatic cancer,however it has not been applied to treat cholangiocarcinoma.We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma,yet no phase 3 trials have been made.CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma.Surgery was performed,followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine;although,the gemcitabine was suspended due to allergic reaction after two cycles.In April 2019,metastatic cholangiocarcinoma relapse was diagnosed,and a first-line treatment with FOLFOX scheme was started.Eight cycles were administered,producing an initial clinical improvement and decrease in blood tumor marker levels.Radiological and serological progression was noted in September 2019.As a second-line treatment,FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea.A combination therapy with gemcitabine was not feasible,as the patient had previously suffered from an allergic reaction to this treatment.We decided to use nab-paclitaxel as a second-line treatment,and four cycles were administered.Both clinical and serological responses were observed,and a radiological mixed response was also noted.CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy,which should be studied in combination with other types of treatment(chemotherapy,fibroblast growth factor receptor inhibitors).

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2

The 2004 discovery of EGFR mutations,followed by ALK rearrangements,ushered in a targeted therapy era for advanced non-small cell lung cancer(NSCLC).Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC.In the last decade,rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies.Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets,including RET,NTRK fusions,c-MET alterations,and activating mutations in KRAS,BRAF,and HER2,all with frequencies greater than 1%.Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development.This review updates the therapeutic arsenal that especially targets those genes.

A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle

The hair follicle is a biological oscillator that alternates growth,regression,and rest phases driven by the sequential activation of the proliferation differentiation programs of resident stem cell populations.The activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling,while regression and resting phases are mainly regulated by Tgf-β/Bmp/Smad activity.A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling pathways.Here we have focused on the role of Endoglin(Eng),a key co-receptor for members of the Tgf-β/Bmp family of growth factors.Using an Eng haploinsufficient mouse model,we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell niches.We further report thatβ-catenin binds to the Eng promoter depending on Bmp signalling.Moreover,we show thatβ-catenin interacts with Smad4 in a Bmp/Eng-dependent context and both proteins act synergistically to activate Eng promoter transcription.These observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback cross-talk between Wnt/β-catenin and Bmp/Smad signals.

ISCHEMIA AND REPERFUSION REDUCE THE ENDOGENOUS BASIC FIBROBLAST GROWTH FACTOR (bF GF) IN RATSKELETAL MUSCLES

Polyclonal antibodies directed against human recombinant basic fibroblast growth factor (bFGF) were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. bFGF immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, including the heparin-containing basal lamina and also in the capillary basal membrane of both normal and wounded muscles, however the signal intensity was much stronger in normal muscles. After 4-hour ischemia, about 40% of skeletal muscle fibers lost their bFGF immunoreactivity. Muscles which experienced 4-hour ischemia and 24 reperfusion had only a weaker bFGF immunoreactivity. The pathological results supported the concept of destroyed cell connection and fiber necrosis in ischemia and reperfused muscles. The mechanisms involved in this reduced concentration of bFGF in wounded muscles included oxygen radical activation, inflammatory response and reduced secretion of endogenous bFGF. These results were only partially compatible with the established mitogenic role of this protein and suggested that a reduction of endogenous FGF may partly contribute to a delay in wound healing.