The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience

IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.     

The efficacy of postoperative pain management with ketorolac for day case oral surgery

The efficacy of the non-steroidal anti-inflammatory analgesic, ketorolac (Toradol), was investigated in 52 day case patients undergoing removal of impacted third molar teeth under intravenous sedation and local analgesia. The study was double-blind, randomized and placebo-controlled. A single 30 mg dose of ketorolac was administered intravenously just prior to induction of sedation with midazolam. Ketorolac was well tolerated and provided good postoperative analgesia. It is suggested that ketorolac is a useful addition to the analgesic armamentarium and appropriately prescribed, provides good pain relief following day case oral surgery.     

Lymphoproliferative response to synthetic V3 loop P18 peptide and HIV-1 envelope glycoprotein among individuals immunized with gp160 candidate vaccines

Because T-cell responses are critical for defense against viral infections, the synthetic P18 peptide (RIQRGPGRAFVTIGK) and active component of gp160 protein has previously been shown to induce cytotoxic and helper T-lymphocyte responses. In order to further define the T-helper cells, responses which are known to play a role in enhancing the immunological response to foreign antigen, we studied the response of individuals immunized with HIV gp160 candidate vaccines. We investigated the proliferative cellular response of peripheral blood mononuclear cells (PBMC) derived from individuals immunized with gp160 antigens in three different protocols. We found a PBMC proliferative response to synthetic P18 peptide in healthy immunized individuals induced by gp160 antigen with or without vaccinia virus. There was correlation between the proliferative response to P18 peptide and other antigens such as HIV-like proteins and gp160 molecule. HLA-DR typing revealed the possible presentation of P18 peptide by several different class II molecules. Since these class II molecules occur frequently in the general population, P18 peptide appears to contain broadly reactive epitopes and thus is presented by mutiple HLA class II molecules. Due to its broad reactivity P18 peptide is one of the candidates for inclusion as a subunit vaccine against HIV-1.     

Auditory evoked phosphenes in optic nerve disease

Five patients with optic neuropathy, four vascular and one demyelinating, are described who each complained of an unusual symptom. Bright flashes of light (phosphenes) occurred in the affected eyes and were evoked by sudden unexpected sounds. Movement of the eye alone did not reproduce the symptom. In all patients the phenomenon was sufficiently prominent to interfere with sleep and was the main complaint of one patient. An anticonvulsant (phenytoin) greatly reduced the frequency and intensity of the phosphene in one patient.     

Cryopreservation of all prezygotes in patients at risk of severe hyperstimulation does not eliminate the syndrome, but the chances of pregnancy are excellent with subsequent frozen-thaw transfers

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post- retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved- thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.      

Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli

We developed a bacterial expression system for the human alpha and beta cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative mitochondrial matrix targeting presequences) were co-expressed in Escherichia coli on one plasmid vector with each cDNA having its own IPTG-inducible promoter. Only negligible amounts of active PCC were measured despite the presence of both alpha and beta subunits as indicated by Western blot analysis and the almost complete biotinylation of the alpha subunit. Co-expression of this plasmid with a second plasmid vector over-expressing the E. coli chaperonin proteins, groES and groEL, resulted in a several hundred-fold increase in PCC specific activity, to a level comparable with that found in crude human liver extracts. PCC was partially purified on monomeric avidin affinity resin and the presence of both alpha and beta subunits was demonstrated, thereby confirming the assembly of both subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC results in propionic acidemia, an autosomal recessive disorder. We used this expression system to characterize one missense mutation previously described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC. This mutation, when expressed in E.coli under the same conditions as that of wild-type PCC, had null activity, despite the presence of assembled alpha PCC and beta PCC subunits. This bacterial expression system can be useful for analysis of either alpha PCC or beta PCC mutations. Our findings indicated that the groES and groEL chaperonin proteins were essential for folding and assembly of the human PCC heteromeric subunits.      

Physical activity modulates the effect of a lipoprotein lipase mutation (D9N) on plasma lipids and lipoproteins

We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity.