Multisystem Inflammatory Syndrome in Neonates Born to Mothers with SARS-CoV-2 Infection (MIS-N) and in Neonates and Infants Younger Than 6 Months with Acquired COVID-19 (MIS-C): A Systematic Review

(1) Introduction: There is an increasing literature describing neonates born to mothers with SARS-CoV-2 infection (MIS-N) and infants infected with SARS-CoV-2 who presented with a severe disease (MIS-C). (2) Methods: To investigate clinical features of multisystem inflammatory syndrome in neonates and infants under six months of age, we used a systematic search to retrieve all relevant publications in the field. We screened in PubMed, EMBASE and Scopus for data published until 10 October 2021. (3) Results: Forty-eight articles were considered, including 29 case reports, six case series and 13 cohort studies. Regarding clinical features, only 18.2% of MIS-N neonates presented with fever; differently from older children with MIS-C, in which gastrointestinal symptoms were the most common manifestation, we displayed that cardiovascular dysfunction and respiratory distress are the prevalent findings both in neonates with MIS-N and in neonates/infants with MIS-C. (4) Conclusions: We suggest that all infants with suspected inflammatory disease should undergo echocardiography, due to the possibility of myocardial dysfunction and damage to the coronary arteries observed both in neonates with MIS-N and in neonates/infants with MIS-C. Moreover, we also summarize how they were treated and provide a therapeutic algorithm to suggest best management of these fragile infants.     

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease

BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS: Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). RESULTS: An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION: Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.     

Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

Background  

N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.     

32例国产人工髋关节翻修手术的临床体会

目的：探讨国产人工髋关节翻修原因。方法：回顾总结32例人工髋关节翻修中发现的问题,分析翻修原因。结果：32例中术前诊断松动16例,脱位4例,深部感染2例,白磨通3例,断柄2例,髋周及股部疼痛4例,股骨柄穿通皮质1例。26例取出假体顺利,6部部分骨长入珍珠面而取出假体困难。25例作全髋置换翻修,4例臼怀松动或位置不良致脱位仅翻修髋臼,1例股骨柄穿通皮质更换双动头,2例因深部感染严重而作单纯假体取出、清创术。全组病例经6个月－5年随访,Harris评分术前平均43分,术后平均81分,平均增加38分。结论：目前翻修病例仍以国产人工关节为主。翻修原因主要是：人工关节质量因素和手术技术因素。造成假体过早松动或种种其它并发症,最终失败。提示国产人工关节质量需改进,需相应配套器械,手术操作技术有待提高。     

Effect of extracorporeal shock wave therapy on osteoblastlike cells

Extracorporeal shock wave therapy has been used increasingly in musculoskeletal disorders although its biologic mechanisms are not understood completely. The current study evaluated the effects of extracorporeal shock wave therapy on human osteoblastlike cells by using an electrohydraulic shock wave generator and comparing three energy levels. (Group A, 14 kV and 0.15 mJ/mm2; Group B, 21 kV and 0.31 mJ/mm2; Group C, 28 kV and 0.40 mJ/mm2; Control Group, no energy) and two total impulses (500, 1000) for each level. At the end of treatment, a reduction by approximately 76% was observed in Group C cell number versus basal value when compared with the other groups. Viability, biochemical activity, and gene expression of cultured cells were evaluated 24 and 48 hours after treatment. The viability test showed a decrease in Group C viability of approximately 54% at both culture times as compared with the other groups. Significant increases in nitric oxide, osteocalcin, and transforming growth factor-beta1 production ranging from 10% to 35% were found in Group A. All treated groups had lower C-terminal procollagen Type I values than the Control Group, but important increases were observed between 24 and 48 hours in all groups except Group C. This particular finding reveals that osteoblast differentiation in Group A is enhanced strongly during the first 24 hours after exposure leading after another 24 hours to an increase in C-terminal procollagen Type I production and consequently in bone matrix deposition. The current study showed that one of the most important aspects to be considered is not the total number of impulses used, but the energy level of the shock waves, therefore confirming that extracorporeal shock wave therapy has a dose-dependent initial destructive effect on cells when the selected energy is higher than 21 kV.     

A Prospective,Randomized Comparison of Modified Pulmonary Vein Isolation Versus Conventional Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation

Modified Pulmonary Vein Isolation in AF Ablation. Introduction: Pulmonary vein isolation (PVI) is the primary ablation therapy in patients with atrial fibrillation (AF). We hypothesized that high dominant frequency (DF) sites (AF nests during sinus rhythm [SR]) adjacent to the PV ostia are associated with the atrial substrate that maintains AF, and PVI incorporating the high‐frequency AF nests may have a higher efficacy. Methods and Results: In a prospective and randomized comparison, 126 symptomatic paroxysmal AF patients that underwent PVI were enrolled. We compared the efficacy of a modified PVI (ablation line: 1.0–1.5 cm from the PV ostium with encircling the AF nests [spectral analysis with DF >70 Hz during SR, Group II]) versus the anatomy‐guided conventional PVI (Group I). In Group II, the DF value along the PV ostium was lower than 70 Hz after the PVI. The primary endpoint was the freedom from symptomatic atrial arrhythmias after a single procedure. We also followed the autonomic function by a time‐domain analysis of the heart rate variability. In both groups, AF nests were observed and electric isolation was successfully obtained in all patients. With a mean duration of 16 ± 6.1 months of follow‐up, Group II had a higher single procedure efficacy without drugs (78.7% vs 66.1%, log‐rank test: P = 0.02), and fewer repeat procedures (6.6% vs 23%; P = 0.04), as compared to Group I. Conclusion: PVI incorporating the high frequency AF nests adjacent to the PV ostia had a better single procedure efficacy. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1155–1162, November 2012)     

Familie mit multipler endokriner Adenomatose (MEA TypI) und einigen zusätzlichen Besonderheiten

Zusammenfassung 3 Generationen mit 37 Mitgliedern einer Familie mit multipler endokriner Adenomatose Typ I (MEA Typ I) wurden anamnestisch und katamnestisch erfaßt. Klinische, biochemische und histologische Befunde wurden zusammengestellt: 20 Personen hatten Erkrankungen oder Befunde, die für eine MEA Typ I charakteristisch sind.Ein Patient (II 1) hatte ein chromophobes Hypophysenadenom, Epithelkörperchen- und Inselzelladenome, eine knotige Kolloidstruma und eine bilaterale knotige Nebennierenrindenhyperplasie. Dies ist das voll ausgeprägte Bild einer MEA Typ I (Wermer-Syndrom). Außerdem hatte er ein medulläres Schilddrüsencarcinom.Bei 14 Familienangehörigen ergaben sich Hinweise auf primären Hyperparathyreoidismus (pHPT), darunter waren 5 Patienten mit Nierensteinen. Die bei 3 Personen exstirpierten Epithelkörperchen erlaubten eine histologische Bestätigung der Diagnose pHPT. Die nach Möglichkeit mehrmals durchgeführte Bestimmung des Calcium- und Phosphatspiegels im Serum spielte eine Hauptrolle bei der Entdeckung von asymptomatischen Trägern des Gens.6 Patienten hatten Magen-Darmulcera: darunter waren 5 Patienten mit sicherem oder wahrscheinlichem pHPT, von denen aber nur einer (II 1) ein Gastrinom und eine Inselzelladenomatose hatte. Drei Patienten hatten eine Pankreatitis, bei zwei von ihnen nachweislich kombiniert mit pHPT. — Zweimal fand sich eine euthyreote Struma, einmal eine hyperthyreote Struma. Zwei Familienangehörige hatten erhöhte Plasmacortisolwerte; Lipome im Unterhautfettgewebe hatten ebenfalls zwei Patienten. Der Befund eines Alpha-1-Antitrypsinmangels (ZZ Phänotyp) bei zumindest 2 Patienten mit pHPT läßt an eine genetisch bedingte Verknüpfung des Defektallels Z mit der MEA Typ I denken. Weitere Familienuntersuchungen sind für eine Beweisführung notwendig.Ein Polyp im Jejunum mit heterotoper Magenschleimhaut (Fundus- und Pylorusdrüsen) ausgekleidet und blutend wurde bei diesem Syndrome noch nicht beschrieben. Der Befund wird von uns als Entwicklungsstörung des Entoderm aufgefaßt. Das bei einem Patienten (II 1) gefundene medulläre Schilddrüsencarcinom zeigt, daß die Trennlinie zwischen MEA Typ I und MEA Typ II nicht immer scharf gezogen ist.