The effect of COVID-19 on general anaesthesia rates for caesarean section. A cross-sectional analysis of six hospitals in the north-west of England.

At the onset of the global pandemic of COVID-19 (SARS-CoV-2), guidelines recommended using regional anaesthesia for caesarean section in preference to general anaesthesia. National figures from the UK suggest that 8.75% of over 170,000 caesarean sections are performed under general anaesthetic. We explored whether general anaesthesia rates for caesarean section changed during the peak of the pandemic across six maternity units in the north-west of England. We analysed anaesthetic information for 2480 caesarean sections across six maternity units from 1 April to 1 July 2020 (during the pandemic) and compared this information with data from 2555 caesarean sections performed at the same hospitals over a similar period in 2019. Primary outcome was change in general anaesthesia rate for caesarean section. Secondary outcomes included overall caesarean section rates, obstetric indications for caesarean section and regional to general anaesthesia conversion rates. A significant reduction (7.7 to 3.7%, p < 0.0001) in general anaesthetic rates, risk ratio (95%CI) 0.50 (0.39-0.93), was noted across hospitals during the pandemic. Regional to general anaesthesia conversion rates reduced (1.7 to 0.8%, p = 0.012), risk ratio (95%CI) 0.50 (0.29-0.86). Obstetric indications for caesarean sections did not change (p = 0.17) while the overall caesarean section rate increased (28.3 to 29.7%), risk ratio (95%CI) 1.02 (1.00-1.04), p = 0.052. Our analysis shows that general anaesthesia rates for caesarean section declined during the peak of the pandemic. Anaesthetic decision-making, recommendations from anaesthetic guidelines and presence of an on-site anaesthetic consultant in the delivery suite seem to be the key factors that influenced this decline.

Improving the success rate of human corneal endothelial cell cultures from single donor corneas with stabilization medium.

Main objective of this study was to improve the success rate of human corneal endothelial cell (hCEC) cultures from single donor corneas. We could show that the use of stabilization medium prior to cell isolation may have a positive effect on the success rate of hCEC cultures from single research-grade donor corneas by allowing growth of otherwise possibly not successful cultures and by improving their proliferative rate. hCEC were obtained from corneo-scleral rims of 7 discarded human research-grade cornea pairs. The Descemet membrane-endothelium (DM-EC) sheets of each pair were assigned to 2 experimental conditions: (1) immediate cell isolation after peeling, and (2) storage of the DM-EC sheet in a growth factor-depleted culture medium (i.e. stabilization medium) for up to 6 days prior to cell isolation. hCEC isolated by enzymatic digestion were then induced to proliferate on pre-coated culture plates. The success rate of primary cultures established from single donor corneas were higher for DM-EC sheets kept in stabilization medium before cell isolation. All cultures (7/7) initiated from stabilized DM-EC sheets were able to proliferate up to the third passage, while only 4 out of 7 cultures initiated from freshly peeled DM-EC sheets reached the third passage. In addition, for the 4 successful paired cultures we observed a faster growth rate if the DM-EC sheet was pre-stabilized prior to cell isolation (13.8 ± 1.8 vs 18.5 ± 1.5 days, P < 0.05). Expression of the phenotypical markers Na+/K+-ATPase and ZO-1 could be shown for the stabilized cultures that successfully proliferated up to the third passage.

A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication.

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.

Unrelated donor marrow transplantation in children: transplant policy and outcome in Leiden Paediatrics SCT-Centre.

The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% > or =grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients > or =10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients.

[Descemet membrane endothelial keratoplasty (DMEK): two-year results]. / Queratoplastia endotelial de membrana de Descemet (DMEK): resultados a dos años.

PURPOSE: To report the two-year results of Descemet membrane endothelial keratoplasty (DMEK) for managing corneal endothelial disorders. METHODS: Non-randomized prospective clinical trial. A DMEK was performed in ten patients with Fuchs' endothelial dystrophy or bullous keratopathy. A 3.5 mm clear corneal incision was made and "under air" DM was stripped off from the posterior stroma. A 9.0 mm diameter, organ cultured donor DM roll was inserted into a recipient anterior chamber, positioned into the posterior stroma and secured by completely filling the anterior chamber with air for 30 minutes. RESULTS: Three eyes showed complete detachment of the tissue; this was managed by a secondary Descemet stripping endothelial keratoplasty procedure. The remaining seven eyes had a best corrected visual acuity of >or=0.7 in three eyes (43%) at one month, in five eyes (71%) at six months, and in six eyes (86%) at one and two years. At six months, the endothelial cell density averaged 2039 (+/-373) cells/mm2 (n=7), at one year 1925 (+/-267) cells/mm2 (n=7) and at two years 1730 (+/-400) cells/mm2 (n=6). CONCLUSIONS: DMEK may provide quick and nearly complete visual rehabilitation. Since the donor tissue can be stripped from donor corneo-scleral rims, the procedure may be readily accessible to most corneal surgeons.

Queratoplastia endotelial de membrana de Descemet (DMEK): resultados a dos años / Descemet membrane endothelial keratoplasty (DMEK): Two-year results

Objetivo: Describir los resultados, dos años despuésde realizar una queratoplastia endotelial demembrana de Descemet (DMEK: Descemet membraneendothelial keratoplasty), para el tratamientode alteraciones del endotelio corneal.Métodos: Estudio clínico prospectivo no randomizado.En 10 pacientes con distrofia endotelial deFuchs o queratopatía bullosa, se practicó unaDMEK. A través de una incisión de 3,5 mm en córneaclara, la membrana de Descemet (MD) delreceptor fue desprendida del estroma posterior enpresencia de aire. Un disco de 9 mm de diámetroenrollado de MD donante preservada, fue insertadoen la cámara anterior del receptor, posicionado encontacto con el estroma posterior corneal y aseguradoen su posición mediante el llenado completode la cámara anterior con aire durante 30 minutos.Resultados: Tres ojos mostraron un desprendimientocompleto del tejido donante, por lo que fueronsometidos posteriormente a una queratoplastiaendotelial con «pelado» de la MD (DSEK: Descemet stripping endothelial keratoplasty). En los sieteojos restantes, se observó una agudeza visual mejorcorregida (AVMC) ≥ a 0,7 en 3 ojos (43%) en el primermes, en 5 ojos (71%) a los seis meses, y en seisojos (86%) al primer y segundo años. A los seismeses, la densidad celular endotelial media fue de2039 (DS: 373) cél/mm2 (n=7), al año de 1925 (DS:267 cél/mm2 (n=7) y a los 2 años de 1730 (DS: 400)cél/mm2 (n=6).Conclusión: DMEK podría proporcionar una recuperaciónrápida y casi completa de la visión. Debidoa que el tejido donante puede ser obtenido a partirde anillos córneo-esclerales donantes, el procedimientopodría ser fácilmente accesible para lamayoría de los cirujanos corneales(AU)

Purpose: To report the two-year results of Descemetmembrane endothelial keratoplasty (DMEK)for managing corneal endothelial disorders.Methods: Non-randomized prospective clinicaltrial. A DMEK was performed in ten patients withFuchs’ endothelial dystrophy or bullous keratopathy.A 3.5 mm clear corneal incision was madeand «under air» DM was stripped off from the posteriorstroma. A 9.0 mm diameter, organ cultureddonor DM roll was inserted into a recipient anteriorchamber, positioned into the posterior stroma andsecured by completely filling the anterior chamberwith air for 30 minutes.Results: Three eyes showed complete detachmentof the tissue; this was managed by a secondary Descemetstripping endothelial keratoplasty procedure.The remaining seven eyes had a best correctedvisual acuity of ≥ 0.7 in three eyes (43%) at onemonth, in five eyes (71%) at six months, and in sixeyes (86%) at one and two years. At six months, theendothelial cell density averaged 2039 (±373) cells/mm2 (n=7), at one year 1925 (±267) cells/mm2(n=7) and at two years 1730 (±400) cells/mm2(n=6).Conclusions: DMEK may provide quick andnearly complete visual rehabilitation. Since thedonor tissue can be stripped from donor corneoscleralrims, the procedure may be readily accessibleto most corneal surgeons(AU)

Floating device for donor corneas in organ culture.

AIM: To introduce a new floating device for donor corneas to avoid accumulation of debris onto the endothelial surface during organ culture and to facilitate handling of the tissue during preservation and surgery. METHODS: From 11 donors, one randomly chosen cornea was stored in organ culture attached to a floating device, while the contralateral cornea was attached to the lid of the phial by a suture ("hanging by suture"). Endothelial cell density (ECD) was evaluated prior to tissue storage and after 2-3 weeks of culture. Furthermore, we compared ECD in a larger group of corneas sent off for transplantation with the device (n = 281) to a historical group of control corneas "hanging by suture" (n = 444). RESULTS: There was no significant difference in ECD between corneas attached to the floating device or "hanging by suture" (n = 11; p > or = 0.1). Similarly, no different ECDs were observed between corneas sent off for transplantation with the device (n = 281) and the historical group of control corneas "hanging by suture" (n = 444) (p > or = 0.1). CONCLUSION: The use of the floating device may not affect tissue quality. Since its introduction, the use of the device has been uneventful and greatly facilitated tissue handling.

Hematopoietic stem cell donor selection: the Europdonor experience.

International collaboration is essential for the optimal selection of unrelated hematopoietic stem cell donors. This review focuses on the benefit of a joint worldwide donor file called Bone Marrow Donors Worldwide and the experience of the Europdonor Foundation in selecting strategies to identify the best human leukocyte antigen-matched donor in the shortest time.

How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more!

Many patients do not reach haematopoietic stem cell transplantation. Shortage of unrelated donors (UDs) is still seen as the main cause. However, with a worldwide UD pool containing more than 8 million donors, it is possible that other impediments are becoming more important. We analysed 549 UD searches for Dutch patients, performed between 1987 and 2000, in order to find the reasons for failure or success to reach transplantation. Between 1996 and 2000, 59% of the patients of Northwest European origin received a graft from an UD with a median time span of 4.4 months from the start of the search. In all, 11% of the patients lacked a compatible donor, while 30% became medically unfit for transplantation. This is in contrast to the patients of non-Northwest European origin for whom UD shortage is still the most important impediment; only 32% were transplanted while 50% lacked a compatible donor. We conclude that the shortage of donors is no longer the biggest constraint in unrelated stem cell transplantation for patients of Northwest European origin. It may be more effective to optimize the chance on transplantation by making the search process more efficient.

The importance of identifying a back-up donor for unrelated stem cell transplantation.

The importance of identifying a back-up donor, once a primary suitable unrelated stem cell donor has been found, is often underestimated. Transplant centres erroneously count on the unrelated volunteer donors to be willing, available and medically fit for actual donation. According to our data, which includes 502 unrelated donor work-up procedures performed for 425 Dutch patients between 1987 and 2002, one of 11 work-ups ended in the primary requested donor failing to donate. Of all donor-related cancellations (N=46), 78% of the procedures were deferred due to medical reasons and 22% due to nonmedical reasons. Most of the donors deferred for medical reasons were female (P=0.005). In 50% of the cases for which a back-up donor was already identified, the patients were transplanted with a delay of less then 2 weeks; when no back-up donor was available, the median delay increased to 18 weeks. We strongly encourage implementing a search for at least one back-up donor in the primary search. Identifying a back-up donor can save precious time and complicated logistic rescheduling.

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients.

Juvenile myelomonocytic leukemia (JMML) is a childhood leukemia for which allogeneic BMT is the only curative therapy. At our pediatric stem cell transplantation unit, we performed 26 BMTs in 23 children (age 0.5-12.7 years). Conditioning was CY/TBI based (1980-1996, n=14) or BU/CY/melphalan based (1996-2001, n=9). Donors were HLA-identical siblings (n=11), unrelated volunteers (n=9) or mismatched family members (n=3). A total of 10 patients survive in CR (median follow-up 6.8 years, range 3.1-22.2 years). Relapse or persistent disease was observed in eight and two patients, respectively. Nine of these patients died, one achieved a second remission following acute nonlymphatic leukemia chemotherapy (duration to date 5.3 years). Transplant-related mortality occurred in four patients. Overall survival at 5 and 10 years was 43.5%. Using T-cell-depleted, one-antigen mismatched unrelated donors was the only significant adverse factor associated with relapse in multivariate analysis (P=0.039, hazard ratio 4.9). Together with a trend towards less relapse in patients with graft-versus-host-disease and in patients transplanted with matched unrelated donors, this suggests a graft-versus-leukemia effect of allogeneic BMT in JMML.

Donor and liability insurance of donor registries, donor centers, and collection centers--recommendations.

The article presents views and recommendations of the World Marrow Donor Association regarding the need for donor and liability insurance for hematopoietic stem cell donor registries, and donor and collection centers.

Cancer risk among female nurses: a literature review.

Some studies have demonstrated increased risk of different cancers among female nurses. A review of relevant papers was made to assess whether the increase is caused by occupational exposures or other factors. A computerized literature search on combinations of the keywords 'nurses', 'occupation', 'hazards', 'cancer' and 'mortality' and related articles was performed. A total of 30 reports were identified from 19 independent studies conducted between 1983 and 2001. The majority of the studies were registry studies, with limited data on employment history and confounding factors. In conclusion, knowledge about exposures and observed excesses of cancer risk give reason to suspect an occupational influence on breast cancer and leukaemia. The grouping together of nurses from different workplaces may camouflage real differences in risk. Future studies should collect information at the individual level about work history and personal risk factors.

Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins.

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.

Pulmonary arterial fibromuscular dysplasia: a rare cause of fulminant lung hemorrhage.

Arterial fibromuscular dysplasia (FMD) represents a collection of noninflammatory and nonatherosclerotic vascular diseases with a poorly understood etiology. Classically occurring in renal and cerebral arteries, this entity has also been reported in coronary, carotid, and other medium and small arteries. One case occurring in the pulmonary vasculature has been reported. Fatal hemothorax and lung hemorrhage have multiple causes, including other vascular malformations and connective tissue disorders; however, cases of pulmonary FMD are exceedingly rare. We report what appears to be the second such association, occurring in a 69-year-old man. The patient presented with a 3-week history of increasing dyspnea, fatigue, and productive cough; 3 days of increasing back and chest pain; and syncope. Chest radiograph showed a "white-out" of the left lung. The patient died shortly after admission from a fulminant respiratory disease of undetermined etiology. At autopsy he was found to have a massive left hemothorax resulting from an unsuspected pulmonary arterial fibromuscular dysplasia.