The quantitative impact of COVID-19 on surgical training in the United Kingdom.

BACKGROUND: COVID-19 has had a global impact on all aspects of healthcare including surgical training. This study aimed to quantify the impact of COVID-19 on operative case numbers recorded by surgeons in training, and annual review of competency progression (ARCP) outcomes in the UK. METHODS: Anonymized operative logbook numbers were collated from electronic logbook and ARCP outcome data from the Intercollegiate Surgical Curriculum Programme database for trainees in the 10 surgical specialty training specialties.Operative logbook numbers and awarded ARCP outcomes were compared between predefined dates. Effect sizes are reported as incident rate ratios (IRR) with 95 per cent confidence intervals. RESULTS: Some 5599 surgical trainees in 2019, and 5310 in surgical specialty training in 2020 were included. The IRR was reduced across all specialties as a result of the COVID-19 pandemic (0.62; 95 per cent c.i. 0.60 to 0.64). Elective surgery (0.53; 95 per cent c.i. 0.50 to 0.56) was affected more than emergency surgery (0.85; 95 per cent c.i. 0.84 to 0.87). Regional variation indicating reduced operative activity was demonstrated across all specialties. More than 1 in 8 trainees in the final year of training have had their training extended and more than a quarter of trainees entering their final year of training are behind their expected training trajectory. CONCLUSION: The COVID-19 pandemic has had a major effect on surgical training in the UK. Urgent, coordinated action is required to minimize the impacts from the reduction in training in 2020.

Motec Wrist Arthroplasty: 4 Years of Promising Results.

BACKGROUND: The Motec cementless modular metal-on-metal ball-and-socket wrist arthroplasty is an implant with promising intermediate results. An alternative to primary wrist fusion, total wrist arthroplasty is an option for active patients, who wish to retain their wrist function. It is indicated in cases of degenerative osteoarthritis, post-traumatic arthritis and rheumatoid (inflammatory) arthritis. METHODS: A prospective review of patient demographics, pre and post-operative Disabilities of the Arm Shoulder and Hand (DASH), MAYO scores, range of movements and grip strengths. All complications in follow up were recorded across the 4 year period. RESULTS: 25 implants on 23 patients over 5.5 years, mean age 61; 8 females and 15 male. 10 patients with SLAC, 3 SNAC, 5 inflammatory and 7 patients with generalized osteoarthritis. The patients showed significant improvements of MAYO and DASH scores post-operatively, as well as the flexion/extension arc and grip strengths. There was just one case of implant loosening- the radial screw after a wound infection, which was revised with a longer screw. Two implants were converted to Motec fusion due to pain. One implant was dislocated and relocated. The remaining patients have had good wrist function. Only 6 patients were unable to return to work. CONCLUSIONS: Similar to published studies, this series shows the Motec implant to be a good motion preserving alternative to total wrist fusion.

Modulation of the heteromeric Kir4.1-Kir5.1 channels by P(CO(2)) at physiological levels.

Several inward rectifier K(+) (Kir) channels are pH-sensitive, making them potential candidates for CO(2) chemoreception in cells. However, there is no evidence showing that Kir channels change their activity at near physiological level of P(CO(2)), as most previous studies were done using high concentrations of CO(2). It is known that the heteromeric Kir4.1-Kir5.1 channels are highly sensitive to intracellular protons with pKa value right at the physiological pH level. Such a pKa value may allow these channels to regulate membrane potentials with modest changes in P(CO(2)). To test this hypothesis, we studied the Kir4.1-Kir5.1 currents expressed in Xenopus oocytes and membrane potentials in the presence and absence of bicarbonate. Evident inhibition of these currents (by approximately 5%) was seen with P(CO(2)) as low as 8 torr. Higher P(CO(2)) levels (23-60 torr) produced stronger inhibitions (by 30-40%). The inhibitions led to graded depolarizations (5-45 mV with P(CO(2)) 8-60 torr). Similar effects were observed in the presence of 24 mM bicarbonate and 5% CO(2). Indeed, the Kir4.1-Kir5.1 currents were enhanced with 3% CO(2) and suppressed with 8% CO(2) in voltage clamp, resulting in hyper- (-9 mV) and depolarization (16 mV) in current clamp, respectively. With physiological concentration of extracellular K(+), the Kir4.1-Kir5.1 channels conduct substantial outward currents that were similarly inhibited by CO(2) as their inward rectifying currents. These results therefore indicate that the heteromeric Kir4.1-Kir5.1 channels are modulated by a modest change in P(CO(2)) levels. Such a modulation alters cellular excitability, and enables the cell to detect hypercapnia and hypocapnia in the presence of bicarbonate.

Distinct histidine residues control the acid-induced activation and inhibition of the cloned K(ATP) channel.

The modulation of K(ATP) channels during acidosis has an impact on vascular tone, myocardial rhythmicity, insulin secretion, and neuronal excitability. Our previous studies have shown that the cloned Kir6.2 is activated with mild acidification but inhibited with high acidity. The activation relies on His-175, whereas the molecular basis for the inhibition remains unclear. To elucidate whether the His-175 is indeed the protonation site and what other structures are responsible for the pH-induced inhibition, we performed these studies. Our data showed that the His-175 is the only proton sensor whose protonation is required for the channel activation by acidic pH. In contrast, the channel inhibition at extremely low pH depended on several other histidine residues including His-186, His-193, and His-216. Thus, proton has both stimulatory and inhibitory effects on the Kir6.2 channels, which attribute to two sets of histidine residues in the C terminus.

Direct activation of cloned K(atp) channels by intracellular acidosis.

ATP-sensitive K(+) (K(ATP)) channels may be regulated by protons in addition to ATP, phospholipids, and other nucleotides. Such regulation allows a control of cellular excitability in conditions when pH is low but ATP concentration is normal. However, whether the K(ATP) changes its activity with pH alterations remains uncertain. In this study we showed that the reconstituted K(ATP) was strongly activated during hypercapnia and intracellular acidosis using whole-cell recordings. Further characterizations in excised patches indicated that channel activity increased with a moderate drop in intracellular pH and decreased with strong acidification. The channel activation was produced by a direct action of protons on the Kir6 subunit and relied on a histidine residue that is conserved in all K(ATP). The inhibition appeared to be a result of channel rundown and was not seen in whole-cell recordings. The biphasic response may explain the contradictory pH sensitivity observed in cell-endogenous K(ATP) in excised patches. Site-specific mutations of two residues showed that pH and ATP sensitivities were independent of each other. Thus, these results demonstrate that the proton is a potent activator of the K(ATP). The pH-dependent activation may enable the K(ATP) to control vascular tones, insulin secretion, and neuronal excitability in several pathophysiologic conditions.

Molecular determinants for the distinct pH sensitivity of Kir1.1 and Kir4.1 channels.

Kir1.1 (ROMK1) is inhibited by hypercapnia and intracellular acidosis with midpoint pH for channel inhibition (pK(a)) of approximately 6.7. Another close relative, Kir4.1 (BIR10), is also pH sensitive with much lower pH sensitivity (pK(a) approximately 6. 0), although it shares a high sequence homology with Kir1.1. To find the molecular determinants for the distinct pH sensitivity, we studied the structure-functional relationship using site-directed mutagenesis. An NH(2)-terminal residue (Lys-53) was found to be responsible for the low pH sensitivity in Kir4.1. Mutation of this lysine to valine (K53V), a residue seen at the same position in Kir1. 1, markedly increased channel sensitivity to CO(2)/pH. Reverse mutation on Kir1.1 (V66K) decreased the CO(2)/pH sensitivities. Interestingly, mutation of these residues to glutamate greatly enhanced the pH sensitivity in both channels. Other contributors to the distinct pH sensitivity were histidine residues in the COOH terminus, whose numbers are fewer in Kir4.1 than Kir1.1. Mutation of two of these histidine residues in Kir1.1 (H342Q/H354N) reduced CO(2)/pH sensitivities, whereas the creation of two histidines (S328H/G340H) in Kir4.1 increased the CO(2)/pH sensitivities. Combined mutations of the lysine and histidine residues in Kir4.1 (K53V/S328H/G340H) gave rise to a channel that had CO(2)/pH sensitivities almost identical to those of the wild-type Kir1.1. Thus the residues demonstrated in our current studies are likely the molecular basis for the distinct pH sensitivity between Kir1.1 and Kir4.1.

Involvement of histidine residues in proton sensing of ROMK1 channel.

ROMK channels are inhibited by intracellular acidification. This pH sensitivity is related to several amino acid residues in the channel proteins such as Lys-61, Thr-51, and His-206 (in ROMK2). Unlike all other amino acids, histidine is titratable at pH 6-7 carrying a positive charge below pH 6. To test the hypothesis that certain histidine residues are engaged in CO(2) and pH sensing of ROMK1, we performed experiments by systematic mutations of all histidine residues in the channel using the site-directed mutagenesis. There are two histidine residues in the N terminus. Mutations of His-23, His-31, or both together did not affect channel sensitivity to CO(2). Six histidine residues are located in the C terminus. His-225, His-274, His-342, and His-354 were critical in CO(2) and pH sensing. Mutation of either of them reduced CO(2) and pH sensitivities by 20-50% and approximately 0.2 pH units, respectively. Simultaneous mutations of all of them eliminated the CO(2) sensitivity and caused this mutant channel to respond to only extremely acidic pH. Similar mutations of His-280 had no effect. The role of His-270 in CO(2) and pH sensing is unclear, because substitutions of this residue with either a neutral, negative, or positive amino acid did not produce any functional channel. These results therefore indicate that histidine residues contribute to the sensitivity of the ROMK1 channel to hypercapnia and intracellular acidosis.