The electrocardiographic manifestations of pectus excavatum before and after surgical correction.

BACKGROUND: Pectus excavatum (PEx) can cause cardiopulmonary limitations due to cardiac compression and displacement. There is limited data on electrocardiogram (ECG) alterations before and after PEx surgical repair, and ECG findings suggesting cardiopulmonary limitations have not been reported. The aim of this study is to explore ECG manifestations of PEx before and after surgery including associations with exercise capacity. METHODS: A retrospective review of PEx patients who underwent primary repair was performed. ECGs before and after surgical correction were evaluated and the associations between preoperative ECG abnormalities and cardiopulmonary function were investigated. RESULTS: In total, 310 patients were included (mean age 35.1 ± 11.6 years). Preoperative ECG findings included a predominant negative P wave morphology in V1, and this abnormal pattern significantly decreased from 86.9% to 57.4% (p < 0.001) postoperatively. The presence of abnormal P wave amplitude in lead II (>2.5 mm) significantly decreased from 7.1% to 1.6% postoperatively (p < 0.001). Right bundle branch block (RBBB) (9.4% versus 3.9%, p < 0.001), rsr' patterns (40.6% versus 12.9%, p < 0.001), and T wave inversion in leads V1-V3 (62.3% vs 37.7%, p < 0.001) were observed less frequently after surgery. Preoperative presence of RBBB (OR = 4.8; 95%CI 1.1-21.6) and T wave inversion in leads V1-3 (OR = 2.3; 95%CI 1.3-4.2) were associated with abnormal results in cardiopulmonary exercise testings. CONCLUSION: Electrocardiographic abnormalities in PEx are frequent and can revert to normal following surgery. Preoperative RBBB and T wave inversion in leads V1-3 suggested a reduction in exercise capacity, serving as a marker for the need for further cardiovascular evaluation of these patients.

Improvement of Metabolic and Histological Changes of Adiposity in Rats by Synthetic Oleoyl Chalcones.

We previously reported that synthetic oleoyl chalcones had a favorable effect to alleviate metabolic consequences of obesity in male SD rats. In this work, we prepared and characterized by spectroscopic tools, a set of six oleoyl chalcones (5a-c, 10 and 11a,b). The comparative effects of the previously prepared oleoyl chalcones and their new synthetic analogs on metabolic and histological changes in obese male SD rats were studied. It was found that the oleoyl chalcones IIIa and IV were the best in improving many metabolic parameters, e. g., FBG, FI, ISI, TG, and total cholesterol. They cured systemic inflammation, through inhibition of the TNF-α and induction of adiponectin production. Moreover, chalcones IIIa and IV alleviated the oxidative stress accompanying obesity through the induction of the antioxidant enzymes GPX, SOD and CAT besides, GSH. Interestingly, chalcones IIIa and IV exerted hepatoprotective potency and ameliorated the manifestations of NAFLD via inhibition of apoptosis and induction of autophagy of hepatic cells. In conclusion, the oleoyl chalcones IIIa and IV were the most effective candidates among the series of synthetic chalcones in correcting body weight and the consequent metabolic and histological changes in adiposity.

Does a high Haller index influence outcomes in pectus excavatum repair?

OBJECTIVE: Severity for pectus excavatum includes Haller index (HI) > 3.25. An extremely high HI (≥8) may influence surgical approach and complications. This study reviews outcomes of patients with high HI after repair. METHODS: A single institution retrospective analysis was performed on adult patients with HI ≥ 8 undergoing pectus excavatum repairs. For outcomes, a propensity score-matched control group with a HI ≤ 4 was utilized. RESULTS: In total, 64 cases (mean age, 33.5 ± 10.9 years; HI, 13.1 ± 5.0; 56% women) were included. A minimally invasive repair was successful in 84%. A hybrid procedure was performed in the remaining either to repair fractures of the ribs (8 patients) and sternum (5 patients) or when osteotomy and/or cartilage resection was required (10 patients). In comparison with the matched cohort (HI ≤ 4), patients with high HI had longer operative times (171 vs 133 minutes; P < .001), more frequently required hybrid procedures (16% vs 2%; P = .005), experienced higher incidences of rib (22% vs 3%; P = .001) and sternal fractures (12% vs 0%; P = .003), and had increased repair with 3 bars (50% vs 19%; P < .001). There were no significant differences between the groups for length of hospital stay or postoperative 30-day complications. CONCLUSIONS: Patients with an extremely high HI can be challenging cases with greater risks of fracture and need for osteotomy/cartilage resection. Despite this, minimally invasive repair techniques can be utilized in most cases without increased complications when performed by an experienced surgeon.

Evolution of Pain Control for Adult Pectus Excavatum Repair.

BACKGROUND: Pain control after minimally invasive repair of pectus excavatum (MIRPE) can be challenging, especially in adult patients undergoing surgical repair. This study reviewed different analgesic modalities used over ≥10 years after pectus repair. METHODS: A retrospective analysis was performed of adult patients (≥18 years) who underwent uncomplicated primary MIRPE at a single institution from October 2010 to December 2021. Patients were classified by analgesic modality used: epidural, elastomeric continuous infusion subcutaneous catheters (SC-Caths), and intercostal nerve cryoablation. Comparisons among the 3 groups were performed. RESULTS: In total, 729 patients were included (mean age, 30.9 ±10.3 years; 67% male; mean Haller index, 4.9 ±3.0). Patients in the cryoablation group required significantly lower doses of morphine equivalents (P < .001) and had overall the shortest hospital stay (mean, 1.9 ±1.5 days; P < .001) with <17% staying >2 days (vs epidural at 94% and SC-Cath at 48%; P < .001). The cryoablation group had a lower incidence of ileus and constipation (P < .001) but a higher incidence of pleural effusion requiring thoracentesis (P = .024). Mean pain scores among groups were minor (<3), and differences were insignificant. CONCLUSIONS: The use of cryoablation in conjunction with enhanced recovery pathways provided significant benefit to our patients undergoing MIRPE compared with previous analgesic modalities. These benefits included a decrease in length of hospital stay, a reduction of in-hospital opioid use, and a lower incidence of opioid-related complications associated with constipation and ileus. Further studies to assess additional potential benefits with long-term follow-up after discharge are warranted.

Revision after prior failed pectus excavatum repair: higher risks and greater complications than primary surgery.

Background: Revision of a prior failed pectus excavatum (PE) repair is occasionally required. These procedures may be technically more complex and have a greater risk of complications. This study was performed to evaluate the outcomes of adult patients undergoing revision procedures. Methods: A retrospective review of adult patients who underwent revision of a prior PE repair from 2010 to 2023 at Mayo Clinic Arizona was performed. Patients were classified by prior procedure [minimally invasive repair of pectus excavatum (MIRPE), Open/Ravitch, and both] and the type of revision procedure performed [MIRPE, hybrid MIRPE, complex hybrid reconstruction, or complex reconstruction of acquired thoracic dystrophy (ATD)]. Outcomes and complications of these groups were analyzed and compared. Results: In total, 190 revision cases were included (mean age was 33±10 years; 72.6% males, mean Haller Index: 4.4±1.8). For the initial repair procedure, 90 (47.4%) patients had a previous MIRPE, 87 (45.8%) patients a prior open repair, and thirteen (6.8%) patients had both. Furthermore, 30 (15.8%) patients had two or more prior interventions. Patients having had a prior MIRPE were able to be repaired with a revision MIRPE in 82.2% of the cases. Conversely, patients with a prior open repair (including those who had both prior MIRPE and open repairs) were much more likely to require complex reconstructions (85%) as none of the ATD patients in this group had an attempted MIRPE. Operative times were shortest in the MIRPE redo approach and longest in the complex reconstruction of the ATD patients (MIRPE 3.5±1.3 hours, ATD 6.9±1.8 hours; P<0.001). The median length of hospital stay was 5 days [interquartile range (IQR), 3.0 days] with the shortest being the MIRPE approach and the longest occurring in the complex reconstruction of the ATD patients [MIRPE 4 days (IQR, 3.0 days); ATD 7 days (IQR, 4.0 days); P<0.001]. Major and minor complications were more frequent in the ATD complex reconstruction group. Preoperative chronic pain was present in over half of the patients (52.6%). Although resolution was seen in a significant number of patients, significant pain issues persisted in 8.8% of the patients postoperatively. Overall, persistent, long term chronic pain was greatest in the post open/Ravitch patient group (open 13.6% vs. MIRPE 3.6%, P=0.02). Conclusions: Revision of a prior failed PE repair can be technically complex with a high risk of complications, prolonged duration of surgery, and lengthy hospitalization. Chronic pain is prevalent and its failure to completely resolve after surgery is not uncommon. The initial failed repair will influence the type of procedure that can be performed and potentially subsequent complications. Even when some recurrences after previous PE surgeries can be repaired with acceptable results, this study demonstrates the importance of proper primary repair due to these increased risks.

Shiga toxin induces tubular membrane invaginations for its uptake into cells.

Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.

Immunomodulatory properties of S- and N-alkylated 5-(1H-indol-2-yl)-1,3,4-oxadiazole-2(3H)-thione.

A series of S- and N-alkylated indolyloxadiazoles 2-7 were prepared. All compounds were tested for their immunomodulatory activity against T-cell proliferation, oxidative burst and cytokine analysis. Compounds 1, 2a, 2b, 2c and 2k demonstrated highly significant (P ≤ 0.005) inhibition on PHA activated T-cell proliferation with IC(50) less than 3 µg/mL concentration, while 3b exert a moderate inhibitory effect with IC(50) 8.6 µg/mL. Among all compounds of the series, only 2h was found to suppress phagocytes ROS production (IC(50) 2.4 µg/mL) in luminol-based chemiluminescence (CL) assay. Compounds 2a-k have stimulatory effect on proinflammatory cytokine predominantly IL-1ß but no effect on IL-4 and NO production indicating that these compounds might have selective inhibitory effect on T-cell proliferation. Cytotoxic effect on T-cell proliferation was tested on NIH-3T3 mouse fibroblast normal cell line. All compounds were found to be free from toxic effects up to 100 µM concentration.

A new synthetic access to 2-N-(glycosyl)thiosemicarbazides from 3-N-(glycosyl)oxadiazolinethiones and the regioselectivity of the glycosylation of their oxadiazolinethione precursors.

Glycosylations of 5-(1H-indol-2-yl)-1,3,4-oxadiazoline-2(3H)-thione delivered various degrees of S- and/or N-glycosides depending on the reaction conditions. S-Glycosides were obtained regiospecifically by grinding oxadiazolinethiones with acylated α-D-glycosyl halides in basic alumina, whereas 3-N-(glycosyl)oxadiazolinethiones were selectively obtained by reaction with HgCl(2) followed by heating the resultant chloromercuric salt with α-D-glycosyl halides in toluene under reflux. On using Et(3)N or K(2)CO(3) as a base, mixtures of S- (major degree) and N-glycosides (minor degree) were obtained. Pure 3-N-(glycosyl)oxadiazolinethiones can also be selectively obtained from glycosylsulfanyloxadiazoles by the thermal S→N migration of the glycosyl moiety, which is proposed to occur by a tight-ion-pair mechanism. Thermal S→N migration of the glycosyl moiety can be used for purification of mixtures of S- or N-glycosides to obtain the pure N-glycosides. The aminolysis of the respective S- or N-glycosides with ammonia in aqueous methanol served as further confirmation of their structures. While in S-glycosides the glycosyl moiety was cleaved off again, 3-N-(glycosyl)oxadiazolinethiones showed a ring opening of the oxadiazoline ring (without affecting the glycosyl moiety) to give N-(glycosyl)thiosemicarbazides. Herewith, a new synthetic access to one of the four classes of glycosylthiosemicarbazides was found. The ultimate confirmation of new structures was achieved by X-ray crystallography. Finally, action of ammonia on benzylated 3-N-(galactosyl)oxadiazolinethione unexpectedly yielded 3-N-(galactosyl)triazolinethione. This represents a new path to the conversion of glycosyloxadiazolinethiones to new glycosyltriazolinethione nucleosides, which was until now unknown.

Minimally invasive repair of pectus excavatum in adults: a review article of presentation, workup, and surgical treatment.

Pectus excavatum (Pex) is one of the most common congenital deformities of the chest wall, with pectus constituting 90% of all chest wall deformities and excavatum being reported in almost 1:400 to 1:1,000 live births with predominant occurrence in males up to five times more than in females. Depending on the severity, presentation varies from mild cosmetic complaints to life limiting cardiopulmonary symptoms. Patients may develop symptoms as they age, and these symptoms may worsen over the years. A technique for minimally invasive repair for pectus excavatum (MIRPE) was introduced with the concept of temporarily implanting metal bars to correct the deformity. This has rapidly become the standard of care for the pediatric and adolescent patients. The use of MIRPE in adults, however, has been slower to adopt and more controversial. This is largely due to the increased calcification and rigidity of the chest wall in adults which can make the repair more complex and lead to a higher risk of complications. We present a literature review of the presentation, workup, and surgical treatment of adult patients with Pex undergoing MIRPE. Adult patients can, with advanced preoperative evaluations and technique modifications, undergo a highly successful repair resulting in symptom resolution and satisfying results.

Risk Factors and Techniques for Safe Pectus Bar Removal in Adults After Modified Nuss Repair.

BACKGROUND: The Nuss repair involves implants designed for removal after 2 to 3 years. Although rare, significant complications can occur with bar removal, and the incidence of these complications may be higher in adults. This study was performed to review complications and risk factors associated with bar removal and discuss strategies to improve operative safety. METHODS: A retrospective study was performed including all patients after pectus excavatum repair who underwent Nuss implant removal at Mayo Clinic Arizona (Phoenix, AZ) from 2013 to 2022. RESULTS: In total, 1555 bars were removed (683 patients; 71% men; median age, 34 years[(range, 15-71 years]). Of the removals, 12.45% of patients had bars placed at outside institutions. Major complications were rare, with bleeding most common (2.05%), followed by pneumothorax (0.88%), infection (0.59%), and effusions (0.44%). Most major bleeding (85.71%) occurred from the bar track during removal and was controlled by packing the track. One patient required subsequent hematoma evacuation and transfusion. Bleeding secondary to lung injury was also successfully controlled with packing. Bar removal in 1 patient with significantly displaced bars required sternotomy and cardiopulmonary bypass as a result of aortic injury. Risk factors identified for bleeding included sternal erosion (P < .001), bar migration (P < .001), higher number of bars (P = .037), and revision of a previous pectus repair (P = 0.001). Bar migration was additionally associated with major complications (P < .001). Older age, although a risk factor for overall complications (P = 0.001), was not a risk factor for bleeding. CONCLUSIONS: Bar removal can be safely performed in most patients; however, significant complications, including bleeding, may occur. Identifying potential risk factors and being prepared for rescue maneuvers are critical to prevent catastrophic outcomes.

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin.

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic alpha,beta-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI-VII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of alpha,beta-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 microM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 microM.

Synthesis of globo- and isoglobotriosides bearing a cinnamoylphenyl tag as novel electrophilic thiol-specific carbohydrate reagents.

The galactosyl donor, 4,6-di-O-acetyl-2,3-di-O-benzyl-D-galactopyranosyl trichloroacetimidate, was efficiently coupled with regioselectively benzylated lactoside acceptors under standard conditions to stereoselectively afford the corresponding globotrioside and isoglobotrioside derivatives in very good yields. These glycosides were smoothly functionalized with a 6-(p-cinnamoylphenoxy)-hexyl tether tag as novel electrophilic thiol-specific carbohydrate reagents. Immobilization of the globotrioside conjugate to Thiopropyl Sepharose 6B for purification of B-subunit of Shiga toxin (StxB) and coupling of a model cysteine-containing protein (StxB-Z(n)-Cys) to the isoglobotrioside conjugate were both performed with high efficiency.