Comparison of outcomes between minimally invasive and median sternotomy for double and triple valve surgery: A meta-analysis

Background

Limited data exists demonstrating the efficacy of minimally invasive surgery (MIS) compared to median sternotomy (MS) for multiple valvular disease (MVD). This systematic review and meta-analysis aims to compare operative and peri-operative outcomes of MIS vs MS in MVD.

Methods

PubMed, Ovid, and Embase were searched from inception until August 2019 for randomized and observational studies comparing MIS and MS in patients with MVD. Clinical outcomes of intra- and postoperative times, reoperation for bleeding and surgical site infection were evaluated.

Results

Five observational studies comparing 340 MIS vs 414 MS patients were eligible for qualitative and quantitative review. The quality of evidence assessed using the Newcastle-Ottawa scale was good for all included studies. Meta-analysis demonstrated increased cardiopulmonary bypass time for MIS patients (weighted mean difference [WMD], 0.487; 95% confidence interval [CI], 0.365-0.608; P < .0001). Similarly, aortic cross-clamp time was longer in patients undergoing MIS (WMD, 0.632; 95% CI, 0.509-0.755; P < .0001). No differences were found in operative mortality, reoperation for bleeding, surgical site infection, or hospital stay.

Conclusions

MIS for MVD have similar short-term outcomes compared to MS. This adds value to the use of minimally invasive methods for multivalvular surgery, despite conferring longer operative times. However, the paucity in literature and learning curve associated with MIS warrants further evidence, ideally randomized control trials, to support these findings.

     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Species differences in histamine receptors in the vas deferens

Histamine, specific H₁-and H₂-receptor agonists in conjunction with specific H₁-and H₂-receptor antagonists and other types of classical antagonists were used to characterize histamine receptors in the vasa deferentia of mice, rats and guinea pigs. The H₁-receptor mediates contraction while the H₂-receptor produces inhibition. There were marked qualitative and quantitative differences in the distribution of the two types of histamine receptors in the vas deferens of different species. Results indicate that mouse and rat vas deferens contain an inhibitory H₂-receptor, but virtually no excitatory H₁-receptor. In contrast, guinea pig vas deferens contained an excitatory H₁-receptor but was essentially devoid of an inhibitory H₂-receptor. The rank order of relative potencies of various agonists as well as the calculated pA ₂ values of cimetidine in the mouse and rat vas deferens suggest that the two species probably have the same H₂-receptor. High concentrations of histamine and 2-methyl histamine have a stimulant action in the mouse and rat vas deferens which was secondary to release of endogenous noradrenaline rather than to the stimulation of an excitatory H₁-receptor.     

A postsynaptic inhibitory histamine H2-receptor in the mouse isolated vas deferens

The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 M depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [³H]-NA evoked by field stimulation or by high K⁺ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H₂-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca²⁺ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg²⁺ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H₂-receptor. The stimulation of H₂-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca²⁺ required for contraction by depressing the influx of Ca²⁺.     

Constitutive activation of the PI3K‐AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome

Kosaki overgrowth syndrome is a recently described syndrome characterized by distinctive facial features, brain white matter lesions, and developmental delay. Germline activating heterozygous PDGFRB mutations have been reported in this condition. Systemic connective tissue‐type findings have been described in some individuals. We describe a 19‐year‐old Caucasian female with a history of hydrocephalus, Dandy–Walker malformation, cervical spine arachnoid cyst, progressive scoliosis, and overgrowth. Her physical exam included distinctive craniofacial dysmorphism, as well as soft and hyperextensible skin. Cardiovascular imaging during adolescence revealed saccular aneurysms in both coronary artery systems and subtle tortuosity of the cervical vertebral arteries. Exome sequencing trio analysis identified a de novo previously reported pathogenic variant in PDGFRB, c.1696T>C (p.[Trp566Arg]). Further functional studies included platelet‐derived growth factor cellular metabolic pathway activity that confirmed the variant causes a constitutive activation of the PI3K‐AKT pathway. This is the first report to characterize the activating nature of this PDGFRB variant. We also highlight the connective tissue findings seen in Kosaki overgrowth syndrome and recommend baseline echocardiographic evaluation in all individuals with this condition with particular emphasis on coronary arteries.     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P<0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.