The impact of protective measures against COVID-19 on the wellbeing of residents in nursing homes and their relatives: a rapid review.

During the COVID-19 pandemic and compared to other population groups, older people were at a heightened risk of developing lethal disease symptoms. Thus, many countries put in place protective measures to protect this "at-risk" population, especially in nursing homes, to limit the number of infections. These measures consisted mostly in the absence of social gatherings, the impossibility for relatives to enter the nursing homes, limitations in group activities, and the ban of group-eating. Although these measures were helpful to mitigate the spread of the disease, they also induced long periods of social isolation for the residents of nursing homes. This could have impacted the wellbeing and quality of life of residents and their relatives, with a possible impact on the overall health of residents. We designed this rapid review to investigate the literature on the impact of COVID-19 protective measures in nursing homes on the quality of life, wellbeing and physical health of residents and their relatives. Our results showed that most of the articles included in the review, either using qualitative or quantitative methods, evidenced a detrimental impact of protective measures on resident's and their relatives' wellbeing. We argue that, in the event of a new pandemic similar to the COVID-19, protective measures should also take into account their psychological impact, and not only their physical impact.

Impact of drains on nausea and vomiting after thyroid and parathyroid surgery: a randomized controlled trial.

OBJECTIVE: Nausea and vomiting are common side effects following thyroid and parathyroid surgery. In a prospective controlled randomized trial, postoperative nausea and vomiting (PONV) and the number of episodes of vomiting were defined as two primary endpoints. We analysed whether the placement of drains after thyroid or parathyroid surgery enhances PONV and/or influences vomiting. PATIENTS AND METHODS: From November 2007 to January 2012, 136 consecutive patients were included for thyroid or parathyroid surgery and were randomly assigned to group A (drain, n = 69) or group B (no drain, n = 67). PONV was assessed with visual analogue scale (VAS; range 0 to 10) measurements. Furthermore, episodes of vomiting as well as analgetic and antiemetic therapies were recorded. Difference in neck circumference was compared pre- and postoperatively. RESULTS: Patients' characteristics did not differ between group A and B. Postoperative VAS values for pain were 2.4 ± 0.3 (group A) and 2.6 ± 0.2 (group B) (p = 0.62), and for nausea 1.4 ± 0.2 (group A) and 1.1 ± 0.2 (group B) (p = 0.57). The relative occurrences of episodes for postoperative vomiting were equal in both groups 0.3 ± 0.1 (p = 1.0). Antiemetic drugs were administered 37 times (group A) and 18 times (group B) (p = 0.099). The total number of treatments of patients with antiemetic drugs was 23 (33.3%) in group A vs. 13 (19.4%) in group B (p = 0.081). The neck circumference postoperatively was significantly larger in group B (p = 0.0025). CONCLUSIONS: Drains after surgery do not enhance postoperative pain, nausea and vomiting. The placement of drains in thyroid surgery is recommended to avoid relevant fluid collection. Drains however may influence the amount of antiemetic drug requirements. TRIAL REGISTRATION: CLINICALTRIALS. GOV IDENTIFIER: NCT01679418.

Combination therapy for multidrug-resistant cytomegalovirus disease.

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.

Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure.

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. METHODS: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). RESULTS: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8). CONCLUSIONS: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

The specialist in regeneration-the Axolotl-a suitable model to study bone healing?

While the axolotl's ability to completely regenerate amputated limbs is well known and studied, the mechanism of axolotl bone fracture healing remains poorly understood. One reason might be the lack of a standardized fracture fixation in axolotl. We present a surgical technique to stabilize the osteotomized axolotl femur with a fixator plate and compare it to a non-stabilized osteotomy and to limb amputation. The healing outcome was evaluated 3 weeks, 3, 6 and 9 months post-surgery by microcomputer tomography, histology and immunohistochemistry. Plate-fixated femurs regained bone integrity more efficiently in comparison to the non-fixated osteotomized bone, where larger callus formed, possibly to compensate for the bone fragment misalignment. The healing of a non-critical osteotomy in axolotl was incomplete after 9 months, while amputated limbs efficiently restored bone length and structure. In axolotl amputated limbs, plate-fixated and non-fixated fractures, we observed accumulation of PCNA+ proliferating cells at 3 weeks post-injury similar to mouse. Additionally, as in mouse, SOX9-expressing cells appeared in the early phase of fracture healing and amputated limb regeneration in axolotl, preceding cartilage formation. This implicates endochondral ossification to be the probable mechanism of bone healing in axolotls. Altogether, the surgery with a standardized fixation technique demonstrated here allows for controlled axolotl bone healing experiments, facilitating their comparison to mammals (mice).

Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion.

Phagocytosis of Histoplasma capsulatum (Hc) yeasts and microconidia by human macrophages (M phi) was quantified by a fluorescence quenching technique. Phagocytosis of unopsonized Hc yeasts by monocyte-derived M phi and human alveolar M phi (AM) was rapid. After 60 min, 79% of cultured M phi and 59% of AM had ingested an average of 9.8 and 11 yeasts/M phi, respectively. In contrast, only 26% of monocytes ingested 4.5 yeasts/cell after 60 min. Phagocytosis of unopsonized microconidia by cultured M phi and by AM was equivalent. Monoclonal antibodies specific for the alpha-chains and beta-chain of the CD18 family of adhesion receptors inhibited the binding of Hc yeasts and microconidia to cultured M phi and AM. Thus, the M phi CD18 complex mediates recognition of both phases of this dimorphic fungus. Disruption of actin microfilaments with cytochalasin D inhibited both attachment and ingestion of yeasts by M phi. In contrast, nocodazole, which prevents polymerization of microtubules, did not inhibit binding or ingestion. Both drugs inhibited ingestion, but neither drug inhibited binding of C3b- and C3bi-coated sheep erythrocytes to complement receptors type one (CR1) or type three (CR3), respectively. Therefore, different signal transducing mechanisms for phagocytosis appear to be triggered by the binding of Hc yeasts to CD18, and by the binding of EC3bi to CD11b/CD18, respectively.

High-dose chemotherapy using BEAM without autologous rescue followed by reduced-intensity conditioning allogeneic stem-cell transplantation for refractory or relapsing lymphomas: a comparison of delayed versus immediate transplantation.

Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy. High-dose chemotherapy (HDC) for tumor debulking followed by reduced-intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) has been advocated as a concept. We previously treated 10 patients (group A) with BEAM chemotherapy followed by delayed RIC HSCT at day 28. We now report on the subsequent 11 patients receiving BEAM followed immediately by fludarabine/total body irradiation and allogeneic HSCT (group B), and compare the outcome to group A patients. Non-hematological toxicity before engraftment was comparable, only gut toxicity was higher in group B. Days in aplasia, days on antibiotics and length of hospital stay were significantly longer in group A. Cumulative incidence of acute (GvHD) >or=grade II and incidence of chronic GvHD were lower in group B. At last follow-up, seven patients in group A were alive, with six of them in complete remission. In group B, nine patients were alive, seven of them in complete remission. No significant difference in estimated 3-year overall survival was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. Allogeneic HSCT with standard BEAM conditioning is a valid alternative for patients with resistant/relapsed lymphoma, which might be considered earlier in the disease course.

Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis.

BACKGROUND: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. METHODS: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. RESULTS: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P =.0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P =.0001). CONCLUSIONS: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplification.

Patterns of her-2/neu amplification and overexpression in primary and metastatic breast cancer.

BACKGROUND: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. METHODS: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). RESULTS: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. CONCLUSIONS: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therapy.

Derivation of a new parametric impulse response matrix utilized for nodal wind load identification by response measurement.

This paper provides new formulations to derive the impulse response matrix, which is then used in the problem of load identification with application to wind induced vibration. The applied loads are inversely identified based on the measured structural responses by solving the associated discrete ill-posed problem. To this end - based on an existing parametric structural model - the impulse response functions of acceleration, velocity and displacement have been computed. Time discretization of convolution integral has been implemented according to an existing and a newly proposed procedure, which differ in the numerical integration methods. The former was evaluated based on a constant rectangular approximation of the sampled data and impulse response function in a number of steps corresponding to the sampling rate, while the latter interpolates the sampled data in an arbitrary number of sub-steps and then integrates over the sub-steps and steps. The identification procedure was implemented for a simulation example as well as an experimental laboratory case. The ill-conditioning of the impulse response matrix made it necessary to use Tikhonov regularization to recover the applied force from noise polluted measured response. The optimal regularization parameter has been obtained by L-curve and GCV method. The results of simulation represent good agreement between identified and measured force. In the experiments the identification results based on the measured displacement as well as acceleration are provided. Further it is shown that the accuracy of experimentally identified load depends on the sensitivity of measurement instruments over the different frequency ranges.

Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.

Allergy to bumblebee venom.

Allergy to bumblebee venom is a rare form of Hymenoptera venom allergy. Because bumblebees are increasingly used for the pollination of greenhouse plants, the prevalence of this Hymenoptera allergy has increased during the past decade. The clinical presentation, diagnosis and therapy of bumblebee venom allergy are similar to other Hymenoptera venom allergies. There is a significant immunological cross-reactivity between bumblebee and honeybee venom. It has been claimed that immunotherapy with honeybee venom can protect patients with bumblebee venom allergy. This concept, however, has been called into question after the finding of bumblebee venom-specific IgE lacking cross-reactivity to honeybee venom, and three cases of bumblebee venom-allergic patients in whom immunotherapy with honeybee venom was unsuccessful. Immunotherapy with pure bumblebee venom has been shown to be effective and safe, and is currently the treatment of choice in individuals who cannot avoid contact with bumblebees. Immunotherapy with honeybee venom, however, should be considered in patients with severe reactions to bumblebee stings and concurrent sensitization to honeybee venom.

High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma.

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.

Relative risk of malignant tumors in analgesic abusers. Effects of long-term intake of aspirin.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) e.g. aspirin, indomethacin are reported in epidemiological and experimental studies to reduce the risk for colo-rectal cancer and potentially other malignant tumors. METHODS: We examined the effect of NSAIDs on tumor prevalence in abusers of mixed analgesics containing aspirin, phenacetine, caffeine or codein. 618 analgesic abusers who were autopsied between 1968-1983 were compared with a control group without evidence of analgesic abuse matched for sex, age and year autopsy was performed. RESULTS AND CONCLUSIONS: Abusers were found to have an overall risk of 0.40 fold of having developed a malignancy as compared with the controls. Excluding patients with urinary tract tumors which are increased in analgesic abusers the risk was further decreased to 0.28. No statistically significant effect was found for patients with prostate cancer. The results encourage prospective control studies in high risk patients.

A comparative study of two methods of controlled mobilization of flexor tendon repairs in zone 2.

This prospective study compares subjects following primary repair of flexor tendons in zone 2 using either controlled active motion or a modified Kleinert regime. A matched pairs design was employed, subjects being matched for gender, age and injury characteristics. Twenty-six pairs of subjects with 92 tendon injuries in 52 digits were assessed 12 weeks postoperatively in respect of range of motion and dehiscence. Outcomes were defined using the Strickland criteria. No statistically significant differences in respect of range of motion were demonstrated between the groups. Incidence of rupture, however, was significantly less in the modified Kleinert group (7.7%) than in the controlled active motion group (46%).

[Therapy of allergic bronchial asthma]. / Therapie des allergischen Asthma bronchiale.

Asthma and atopy are strongly related conditions. The presence of specific IgE to perennial (arthropods, animal dander and other), seasonal (pollens, certain fungal spores) and occupational allergens is associated with the occurrence of asthmatic symptoms. Current therapy is based on combining three principles: Avoidance of trigger factors and of allergen exposure, drug therapy, and specific immunotherapy. Feasability and effectiveness of allergen avoidance (particularly of perennial allergens) have been proven. However, these measures must often be supplemented with drug therapy. Several classes of drugs are nowadays available for treatment of asthmatic symptoms and, most importantly, for control of the bronchial inflammatory process which underlies atopic asthma. Specific immunotherapy is a good treatment option in allergy to pollens, but its use is controversial in allergy to house dust mites and other perennial allergens. Finally, it should be kept in mind that the successful longterm management of patients with atopic asthma depends highly on the compliance of patients.

[Diagnostic and therapeutic aspects of the initial epileptic seizure]. / Diagnostische und therapeutische Aspekte des erstmaligen epileptischen Anfalls.

We present the concept of an 'epileptic syndrome' which is important for prognostic statements and the application of appropriate therapeutic measures. We then discuss the epileptic seizure and the assessment of suspected seizure, indications for admission to a hospital, diagnostic measures (EEG, CT scan, laboratory tests, lumbal puncture, MRI scan, PET scan, angiography), therapy and procedures for imminent status epilepticus. Finally, we try to answer the question whether anticonvulsant medication should be instituted after a first epileptic seizure.

GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM.

There is increasing evidence suggesting that both angiogenesis and endothelial injury are involved in GVHD. To study the dynamics of angiogenesis, we examined 26 patients with AML who had undergone allogeneic haematopoietic SCT. All were in CR and had either acute GVHD (aGVHD) or chronic GVHD (cGVHD). We performed immunohistochemical studies of BM microvessel density (MVD) using Abs against vascular-endothelial (VE)-cadherin, CD34 and CD105, and expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2. At the time of diagnosis, the MVD in AML patients was higher than that in the normal controls, and the MVD decreased after induction chemotherapy. Patients with aGVHD had a significantly higher MVD than patients without aGVHD. Conversely, patients with cGVHD did not have a significantly different MVD. In previous aGVHD, we also found more VEGF+ megakaryocytes. XY FISH in sex-mismatched patients showed that the BM blood vessels consisted mainly of recipient endothelial cells. Taken together, these results suggest that new vessel formation and the VEGF/VEGFR system are involved in aGVHD.