Epidemiological link between obesity,type 2 diabetes mellitus and cancer

There exists a complex interaction between obesity, type 2 diabetes mellitus (T2DM) and cancer, and an increase in the incidence of cancer is expected with the growing obesity-diabetes pandemic. The association of cancer with diabetes mellitus and obesity appears to be site-specific, the highest risk being for post-menopausal breast cancer, endometrial cancer, and colorectal cancer. Moreover, there is worsening of hyperglycaemia with the onset of cancer, evidencing a bi-directional link between cancer and diabetes mellitus and the need for monitoring for diabetes in cancer survivors. In this review, we look at the epidemiological evidence from observational studies and Mendelian randomization studies linking obesity, diabetes, and cancer, as well as the complex pathophysiological mechanisms involved, including insulin resistance with associated hyperinsulinaemia, the effect of chronic low-grade inflammation, and the effect of various adipokines that are associated with obesity and T2DM. Additionally, we describe the novel therapeutic strategies, based on their role on the discrete pathophysiological mechanisms involved in the tumourigenesis.     

Long-Term Outcomes of Everolimus Therapy in De Novo Liver Transplantation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundRisk of nephrotoxicity in liver transplant patients on calcineurin inhibitors (CnIs) is a concern. Several controlled trials reported benefit of everolimus (EVR) in minimizing this risk when combined with a reduced CnI dose.BackgroundTo systematically review the efficacy and safety of EVR, alone or with reduced CnI dose, as compared to CnI alone post-liver transplantation.MethodsWe searched MEDLINE, Scopus, and the Cochrane Library for randomized controlled trials comparing EVR- and CnI-based regimens post-liver transplantation. Assessment of studies and data extraction were undertaken independently.ResultsEight studies were selected, describing 769 patients. Cockcroft-Gault GFR was higher at one (P = .05), 3, and 5 years (P = .030) in patients on EVR compared to those receiving CnI therapy. The composite endpoint of efficacy failure was similar between the 2 arms after 1, 3, and 5 years of study. More patients discontinued EVR due to adverse effects in 1 year; however, no difference was noted after 3 or 5 years. A higher rates of proteinuria, peripheral edema, and incisional hernia occurred in patients on EVR.ConclusionsThe analysis confirms noninferiority of EVR and reduced CnI combination. Combination regimen resulted in better renal function compared to standard CnI therapy.     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

Recovery of motor and language abilities after stroke: the contribution of functional imaging

In recent years, functional imaging techniques, like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and transcranial magnetic stimulation (TMS), have shown that the improvement of motor and language function after ischemic stroke is accompanied by extensive reorganizational changes in the human cortex. To better understand these changes and to judge to what extent they could be responsible for clinical improvement, some basic principles of the organization of the motor and language system are discussed.Non-invasive functional imaging can have only a limited contribution in determining which of the possible underlying neural mechanisms, as they are known from animal experiments, play a role in functional recovery. However, they make it possible to define the functional consequences of anatomical lesions in individual patients and to correlate these functional consequences in the motor and language system with the clinical deficit. They can be used to assess the influence on the cortical reorganization of established and newer physiotherapies, logopedics and medical intervention, and they could be a useful tool in determining prognosis.     

Interleukin-6 and selected plasma proteins in healthy persons of different ages

In the present study, interleukin-6(IL-6) and several acute phase proteins were measured in healthy participants (23–87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml(00.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction.     

Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in cushing's disease and Nelson's syndrome

Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear.     

Progress in the treatment of congenital malformations of the hand

Treatment of congenital malformations of the hand and forearm has progressed not only from new procedures, but especially due to a new technique, namely microsurgery. Microsurgery enables skilled hand surgeons to operate on the tiny hands of babies without damaging the anatomical structures. The optimal time for the correction of many deformities is during the first 2 years of life. This gives excellent adaptation of the corrected structures to their altered function, especially in combination with a long period of further growth. Several new procedures are described which have been made possible only since the introduction of microsurgery, either by microvascular anastomoses or by meticulous dissection technique (toe transplantation, proximal toe phalanx transplantation, nail wall formation in complex syndactyly, transposition of digital parts in polydactyly and radial club hand).

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Resumen El tratamiento de las malformaciones congénitas de la mano y el antebrazo ha progresado no sólo en términos de nuevos procedimientos, sino, especialmente, en razón de una nueva técnica, la microcirugía. La microcirugía permite que los cirujanos de mano idoneos puedan operar sobre las pequeñas manos de bebés sin causar daño a las estructuras anatómicas. La época óptima para la corrección de muchas deformaciones es durante los 2 primeros años de vida. Esto hace posible una excelente adaptatión, de las estructuras que han sido corregidas a la función alterada, especialnmente durante períodos prolongados del crecimiento. Se describen algunos nuevos procedimientos que han sido factibles sólo desde la introducción de la microcirugía, bien sea por anastomosis microvascular o por una meticulosa técnica de disecci [trasplante de un artejo, transplante de la falange proximal, formación de la uña en sindatilia compleja, transposición de partes de dígitos en polidactilia y en mano zamba radial (club hand)].

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Résumé Le traitement des malformations congénitales de la main et de l'avant-bras a progressé non seulement grâce à de nouveaux procédés mais surtout grâce à l'apparition de toute une technique nouvelle: la microchirurgie. Celle-ci permet à des chirurgiens de la main expérimentés d'opérer les toutes petites mains des jeunes enfants sans compromettre la fonction des structures anatomiques. Les 2 premières années de la vie sont la meilleure période pour corriger la plupart des malformations: elles permettent une adaptation excellente des structures de fonction auparavant altérée, en se combinant avec la longue période de croissance à venir. Plusieurs procédés nouveaux sont répertoriés. Ils sont devenus possibles seulement depuis l'introduction de la microchirurgie: il s'agit notamment des anastomoses microvasculaires ou des techniques méticuleuses de dissection comme le transfert d'orteil ou de la phalange proximale de l'orteil, la création du mur latéral d'ongle dans un cas de syndactylie complexe ou la transposition de segments des doigts pour polydactylie ou main bote radiale.

     

Factors associated with insomnia symptoms: A cross-sectional study during a Covid-19 fully restrictive lockdown

Insomnia is the most frequent sleep disorder and a public health concern that increased during the Covid 19 pandemic. Fully restrictive lockdowns during Covid are interesting periods to examine the impact of environmental and behavioural changes on the emergence of insomnia symptoms. In this cross-sectional study we aimed to (1) determine the main factors associated with insomnia symptoms during a Covid-19 fully restrictive lockdown examining the associated daily life alterations and (2) create a predictive model of insomnia symptoms. We used the data drawn from the “Covid-RythmE” study that reached volunteers from the general French population through an online survey during the last 2 weeks of the 2 month full lockdown. Associations with insomnia symptoms were tested and significant associations were entered in a Backward Stepwise Logistic Regression (BSLR) to assess the best combination to classify individuals with or without insomnia symptoms. From the 1624 participants, 50.64% suffered from mild to severe insomnia symptoms as assessed by the ISI. The best combination for explaining insomnia symptoms with 74.26% of accuracy included: age (OR = 1.15), females (OR = 1.26), smaller home sizes (OR = 0.77), environmental noises (OR = 1.59), anxiety symptoms (OR = 1.24), depressive symptoms (OR = 1.15), regularity of sleep–wake schedules (OR = 1.25), exposure to screen during the morning (OR = 1.13), and LED light during the evening (OR = 1.17). Thus, lifestyle schedule and exposure to natural synchronizers such as light, are primordial in considering in insomnia physiopathology, prevention and treatment, as well as the associated mental health status.