ADAMTSL2 is a potential prognostic biomarker and immunotherapeutic target for colorectal cancer: Bioinformatic analysis and experimental verification.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Syncope and driving, flying and vocational concerns.

When advising a syncope patient about resumption of driving, flying or vocational activities, physicians must consider relevant laws and regulations, the etiology of the syncope, and the risk of recurrence and the impact of recurrence on the safety of the patient and others. Guidelines from professional cardiology societies may aid the physician. In the United States, private driving is regulated by individual states and their laws show significant variance. Commercial driving and flying are regulated at the federal level. These regulations tend to be more uniform, but are significantly stricter due to the potential risk to the public posed by commercial drivers or pilots with syncope. For many diagnoses, both regulations and professional society recommendations incorporate an observation period following the index syncopal event. This is due to the natural history of syncope recurrence and to allow time to monitor the response to treatment.

[Treatment of chronic osteomyelitis of tibia with debridement and vacuum sealing drainage (VSD) of cavitas medullaris].

OBJECTIVE: To explore the therapeutic effect of debridement and vacuum sealing drainage (VSD) of cavitas medullaris for the treatment of chronic osteomyelitis of tibia. METHODS: From March 2006 to May 2009, 19 patients with chronic osteomyelitis of tibia were treated by debridment and VSD, then the second operation were performed to close the wound. Among them, 12 patients were male and 7 patients were female, the average age was 39 years (ranged from 25 to 68 years). The course of disease were from 10 months to 5 years. The main clinical symptoms were red swelling, tenderness and fluid of local soft tissue. There were prolonged unhealed sinus and pus; the X-ray showed osteosclerosis, increased bone mineral, and sequestrum and dead space was formed. The result of bacterial culture showed 3 cases were aeruginosus bacillus, 13 cases staphylococcus aureus, 1 case bacillus aerogenes and 2 cases beta streptococcus. Among them, 3 cases were methicillin resistant staphylococcus (MRS). RESULTS: After debridement and VSD of cavitas medullaris 18-22 days later, the granulation tissue grow well and the wounds of the 19 patients all healed primarily with direct suturing of 17 cases, loco-regional flap of 2 cases. The standard of wound healing was the dryness, cleanness and no drainage. The X-ray revealed the bone tissue grew well and no relapse and fracture occurred during followed-up 6-12 months. CONCLUSION: The debridement and VSD of cavitas medullaris is a very effective and safe treatment for chronic osteomyelitis of tibia.

Effect of medical therapy on left ventricular ejection fraction in patients with systolic heart failure and narrow QRS duration with and without ischemic heart disease and left ventricular mechanical dyssynchrony.

We studied 99 consecutive patients with class III-IV systolic heart failure with a left ventricular ejection fraction (LVEF) < or =35% and a QRS duration <120 milliseconds. Patients with cardiac resynchronization therapy were excluded. Echocardiography was performed in all patients before and after optimal standard heart failure therapy. The septal-to-posterior wall motion delay (SPWMD) > or =130 milliseconds on echocardiogram was defined as left ventricular mechanical dyssynchrony (LVMD). Sixty-nine of 99 patients (70%) had ischemic heart disease. During follow-up of 15.2 +/- 9.8 months, LVEF improvement > or =15% was greater patients in nonischemic group (50%, 15/30) than in ischemic group (9%, 6/69; P < 0.001). After adjustment for age, gender, and clinical and echocardiographic characteristics, ischemic heart disease and grade of coronary disease were persistently related to LVEF improvement > or =15% (P = 0.03 and 0.02, respectively). Twenty of 99 patients (20%) had SPWMD > or =130 milliseconds (LVMD group), and 79 of 99 patients (80%) had SPWMD <130 milliseconds (non-LVMD group). LVEF increased in both groups (P = 0.005) during follow-up, but the percentage of patients with LVEF improvement > or =15% in LVMD was greater compared with patients without LVMD (40% versus 16%, respectively, P = 0.03). In conclusion, the improvement of LVEF in patients with systolic heart failure and narrow QRS was greater in patients with nonischemic heart disease and LVMD compared with patients with ischemic heart disease and absence of LVMD during medical therapy without cardiac resynchronization therapy.

Thromboembolism in patients with atrial fibrillation with and without left atrial thrombus documented by transesophageal echocardiography.

The incidence of cerebrovascular events (CVEs) was investigated in 95 consecutive patients with atrial fibrillation (AF) with left atrial thrombus (LAT) diagnosed by transesophageal echocardiography (TEE) and in 131 age- and sex-matched AF patients without LAT. Compared with patients without LAT, patients with LAT had a larger left atrial diameter (49 versus 44 mm, P < 0.0001), a lower left ventricular ejection fraction (40% versus 50%, P < 0.0001), a higher prevalence of spontaneous echocardiographic contrast (88% versus 25%, P < 0.001), a reduced left atrial appendage emptying velocity (0.25 versus 0.41 cm/s, P < 0.0001), and less use of antiarrhythmic drugs (61% versus 76%, P = 0.03). Before TEE, the prevalence of prior CVE was higher in LAT patients (20%) compared with patients without LAT (8%) (P = 0.01). Fifty-four of 95 LAT patients (57%) and 81 of 131 non-LAT patients (62%) were on warfarin before TEE. The incidence of prior CVE in LAT patients without warfarin (32%) was higher than that in non-LAT patients without warfarin (10%) (P = 0.02). The mortality rate in LAT patients with an international normalized ratio (INR) >or= 2.0 (42%) was higher than that in patients without LAT and an INR >or= 2.0 (11%) (P < 0.001). Fifty-one of 95 LAT patients (54%) underwent repeat TEE before cardioversion (48 patients received warfarin therapy). The thrombus resolved in 40 of 51 patients (78%) after the first TEE. There was no significant difference in INR between the patients with persistent and resolved LAT. AF patients with persistent LAT had a higher incidence of CVE (45%) than the patients with resolved LAT (5%) (P = 0.003). We suggest that patients with LAT be treated with warfarin to maintain an INR between 2.5 and 3.5 rather than between 2.0 and 3.0 because they are at a high risk for new thromboembolism.

Cardiac resynchronization therapy in patients with intrinsic and right ventricular pacing-induced left bundle branch block pattern.

We studied 95 consecutive patients, mean age 70 years, who received cardiac resynchronization therapy (CRT) for class III or IV heart failure with a left ventricular (LV) ejection fraction < or =35% and a QRS duration > or =120 ms. Sixty-seven patients had intrinsic left bundle branch block (LBBB) (group 1), and 28 patients had right ventricular pacing-induced LBBB (group 2). The time difference (TPW-TDI) between onset of QRS to the end of LV ejection by pulsed wave Doppler and onset of QRS to the end of systolic wave in the basal segment with greatest delay by tissue Doppler imaging was measured before CRT and at the last follow-up after CRT. TPW-TDI >50 ms was defined as left ventricular mechanical dyssynchrony. A positive response to CRT was defined as LV volume at end-systole decreasing > or =15% after CRT. The percentage of CRT responders in group 2 was significantly greater than that in group 1 (68% versus 42%, P = 0.04) during follow-up of 16 months. After adjusting for age, gender, and clinical features, this pattern of CRT response persisted (P = 0.008). Similarly, there was a greater reduction in QRS duration in group 2 (178 ms) after CRT versus 154 ms for group 1, P = 0.01. There was no significant difference in TPW-TDI between the 2 groups at baseline or at follow-up. There was no significant difference in mortality (15% versus 14%) and Kaplan-Meier survival plot during follow-up. Patients with heart failure and right ventricular pacing-induced LBBB have a better response rate to CRT than patients with intrinsic LBBB. The change in left ventricular mechanical dyssynchrony after CRT was similar in these 2 groups of patients.

Warfarin therapy initiated before is more beneficial than after transesophageal echocardiography detected left atrial thrombus.

OBJECTIVE: Warfarin anticoagulation significantly reduces the risk of thromboembolism in patients with atrial fibrillation (AF). However, there are many patients with AF who begin anticoagulation only after left atrial thrombus (LAT) is detected by transesophageal echocardiography (TEE). The impact of anticoagulation in these patients has not been clearly described. The purpose of this study was to investigate the incidence of cerebrovascular accident (CVA) among AF patients who began warfarin before LAT was detected by TEE compared to those who began warfarin only after TEE demonstrated LAT and those did not receive warfarin at any point. METHOD: Of the 90 consecutive AF patients with LAT (male 48, female 42, age 71.5 +/- 10.1 years), 49 began warfarin more than 3 weeks before TEE (Group I); 29 began warfarin after TEE (Group II); and 12 did not receive warfarin at all (Group III). RESULTS: The incidence of CVA in Group I (14%, 7/49, prior CVA 5, new CVA after TEE 2) was significantly lower than Group II (45%, 13/29, prior CVA 10, new CVA after TEE 3, P = 0.006) and III (42%, 5/12, prior CVA 3, new CVA after TEE 2, P = 0.047). Patients with persistent LAT had significantly higher incidence (64% vs 23%, P = 0.024) of CVA and lower CVA free survival than those with resolved LAT. CONCLUSION: The incidence of CVA among AF patients, who began warfarin before LAT detection, is significantly lower than those who began warfarin after LAT detection as well as those who did not receive warfarin at all.

Pacemaker utilization during permanent atrial fibrillation in patients who received pacemaker implantation for sinus node dysfunction.

Patients who have pacemakers and sinus node dysfunction frequently have atrial fibrillation (AF). The need for continued pacemaker therapy after conversion to permanent AF remains uncertain. This study showed that, among 174 patients who received pacemaker implantation for sinus node dysfunction, 38% (n = 62) had the minimum intrinsic ventricular rate of >60 beats/min after conversion to AF. The pacemaker memory showed that 30 patients (18%) never used ventricular pacing during permanent AF. The study results suggest that patients who have a stable intrinsic ventricular rate during permanent AF by serial assessment may no longer need continued pacemaker therapy.

The impact of povidone-iodine pocket irrigation use on pacemaker and defibrillator infections.

BACKGROUND: Infection is a devastating complication of permanent pacemakers (PMs) implantable cardioverter defibrillators (ICDs). Many implanting physicians commonly use povidone-iodine solution to irrigate the device pocket before implanting the device. We sought to assess if such a measure would alter the rate of infection. METHODS: A total of 2,564 consecutive patients who received implantable PM or ICD devices between 1994 and 2002 were studied. Povidone-iodine was used for pocket irrigation in 53% and saline in 47%. A total of 18 (0.7%) patients developed pocket infections with 0.7% (10/1,359) in povidone-iodine (group I) and 0.6% (8/1,205) in saline (group II) pocket irrigation (p = ns). Groups I and II were studied for various clinical and demographic variables described in the results section. RESULTS: There was no statistical difference in the baseline demographic and clinical characteristics between groups I and II, respectively. ICDs were most frequently infected than PMs (56% vs 44%). Most (83%) of the devices were dual chamber. Reopening of the pocket for either lead or generator replacement had a higher incidence of infection than new implants (61% vs 39%). There was no difference in the use of preimplantation antibiotic prophylaxis. Late (61%) and deep pocket infections (78%) were more common than early (39%) and superficial infections (22%). Blood cultures were positive in 67% and Staphylococcus aureus was the common most pathogen (50%). The mean duration of antibiotics use after the diagnosis of device infection was 35 +/- 23 days with 72% requiring device explantation. The device was reimplanted on the contralateral side in 56% cases. One patient in each group died due to device infection and related complications. No significant allergy to iodine was seen in either group. CONCLUSION: Povidone-iodine irrigation of the subcutaneous pocket did not alter the rates of pocket infection after pacemaker/defibrillator implantation.

Comparison of recurrence rates after direct-current cardioversion for new-onset atrial fibrillation in patients receiving versus those not receiving rhythm-control drug therapy.

The AFFIRM investigators have recommended rate control as the preferred strategy for recurrent atrial fibrillation (AF), but the appropriate strategy for new-onset persistent AF is uncertain. Our study evaluated the AF recurrence rate and the impact of rhythm-control drugs (class 1A, 1C, and 3 antiarrhythmic drugs) on patients with new-onset persistent AF after successful direct-current (DC) cardioversion. Consecutive patients who underwent DC cardioversion of AF from January 1, 1996 to December 31, 1999 were screened for new-onset persistent AF, and 150 patients met the inclusion criteria. After the first DC cardioversion, 50 patients received rhythm-control drugs (rhythm-control group) and the other 100 did not (rate-control group). The 2 groups had similar clinical characteristics except for a lower ejection fraction (44 +/- 14% vs 49 +/- 14%, p <0.01) and a higher proportion of idiopathic dilated cardiomyopathy (20% vs 1%, p = 0.03) in the rhythm-control group versus the rate-control group. During the follow-up period there was a trend toward a lower rate of early AF recurrence at 24 hours after DC cardioversion in the rhythm-control group versus the rate-control group (6% vs 16%, p = 0.11), but there was a high recurrence rate of AF in both groups at 1 month (30% for the rhythm-control group vs 41% for the rate-control group, p = 0.25). At the end of the follow-up period, rhythm-control therapy was abandoned in 78% of the rhythm-control group patients after the failure of 1 to 3 rhythm-control drugs. In the rate-control group, rhythm-control therapy was attempted after AF recurrence in 62 patients but was later abandoned in 48 patients (77%) because of treatment failure. Therefore, the high incidence of treatment failure with rhythm-control therapy suggests that rate control with anticoagulation should be preferred in patients with new-onset persistent AF if AF recurs after DC cardioversion.

Transesophageal echocardiography before cardioversion of recurrent atrial fibrillation: does absence of previous atrial thrombi preclude the need of a repeat test?

BACKGROUND: Atrial fibrillation (AF) is a recurrent problem that frequently requires repeat cardioversion. Transesophageal echocardiography (TEE) is indicated before cardioversion in patients who are underanticoagulated (warfarin therapy <3 weeks or international normalized ratio [INR] <2.0). It remains uncertain if TEE should be repeated in underanticoagulated patients who had no atrial thrombi detected by previous TEE. Methods and results From January 1996 to June 2001, 76 patients (43 men, 33 women; mean age, 68.8 +/- 10.4 years) who were underanticoagulated and had no atrial thrombi in previous TEE underwent repeat TEE before cardioversion of recurrent AF. The duration of recurrent AF at the time of the second TEE was 5.1 +/- 9.3 months (1 day to 4 years). The underlying diseases included coronary artery disease (n = 30), hypertension (n = 22), valvular heart diseases (n = 8), dilated cardiomyopathy (n = 4), hypertrophic cardiomyopathy (n = 2), and others (n = 10). Eight (10.5%) patients (2 men, 6 women; mean age, 68.6 +/- 6.6 years) were found to have intra-atrial thrombi on the second TEE. Of these 8 patients, 3 had coronary artery disease, 1 had hypertension, 2 had dilated cardiomyopathy, 1 had hypertrophic cardiomyopathy, and 1 had AF of unknown cause. The duration of recurrent AF in patients with and without thrombi was not significantly different (3.6 +/- 4.7 versus 5.3 +/- 9.7 months, P =.22). Of the 8 patients with intra-atrial thrombi on the second TEE, 5 had been taking warfarin for 3 to 4 weeks but had subtherapeutic INR and 3 were taking aspirin only. Compared with patients without intra-atrial thrombi, patients with intra-atrial thrombi had lower ejection fraction (32.5% +/- 18.1% versus 49.9% +/- 14.1%, P =.015), slower left atrial appendage empty velocity (0.22 +/- 0.08 versus 0.41 +/- 0.17 m/s, P <.01), and higher prevalence of spontaneous echo contrast (87.5%) than in patients without intra-atrial thrombi (19.1%, P <.05) but similar left atrial size (49.5 +/- 5.3 versus 47.3 +/- 7.1 mm, P =.15). Cardioversion was cancelled in all patients with atrial thrombi. CONCLUSIONS: In underanticoagulated patients, repeat TEE is necessary before cardioversion of recurrent AF even if the previous TEE showed no atrial thrombi.