Perforator versus Non-Perforator Flap-Based Vulvoperineal Reconstruction-A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with advanced vulvoperineal cancer require a multidisciplinary treatment approach to ensure oncological safety, timely recovery, and the highest possible quality of life (QoL). Reconstructions in this region often lead to complications, affecting approximately 30% of patients. Flap design has evolved towards perforator-based approaches to reduce functional deficits and (donor site) complications, since they allow for the preservation of relevant anatomical structures. Next to their greater surgical challenge in elevation, their superiority over non-perforator-based approaches is still debated. METHODS: To compare outcomes between perforator and non-perforator flaps in female vulvoperineal reconstruction, we conducted a systematic review of English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series. Data on demographics and surgical outcomes were extracted and classified using the Clavien-Dindo classification. We used a random-effects meta-analysis to derive a pooled estimate of complication frequency (%) in patients who received at least one perforator flap and in patients who received non-perforator flaps. RESULTS: Among 2576 screened studies, 49 met our inclusion criteria, encompassing 1840 patients. The overall short-term surgical complication rate was comparable in patients receiving a perforator (n = 276) or a non-perforator flap (n = 1564) reconstruction (p* > 0.05). There was a tendency towards fewer complications when using perforator flaps. The assessment of patients' QoL was scarce. CONCLUSIONS: Vulvoperineal reconstruction using perforator flaps shows promising results compared with non-perforator flaps. There is a need for the assessment of its long-term outcomes and for a systematic evaluation of patient QoL to further demonstrate its benefit for affected patients.

High Expectations Among Patients Who Have Undergone TKA Do Not Correlate With Satisfaction.

BACKGROUND: One of five patients is dissatisfied with the outcome of TKA. With the increasing number of TKAs, this affects many patients. It has been suggested that high expectations may influence satisfaction, but the relationship between preoperative patient expectations and postoperative patient satisfaction remains poorly understood. QUESTIONS/PURPOSES: (1) Are preoperative patient expectations correlated with postoperative satisfaction? (2) Are expectations correlated with patient characteristics or patient-reported outcome measures (PROMs)? (3) Is satisfaction correlated with patient characteristics or PROMs? (4) Do patients report specific items as more relevant to their expectations? METHODS: This was a single-center, observational, retrospective, comparative study involving patients who underwent TKA. Between December 2020 and June 2022, three senior surgeons performed 306 TKAs. Of these, 76% (234) had the preoperative PROMs required for this study, and of these, 82% (193) had completed PROMs at the 12-month follow-up interval and were analyzed. Of the 193 included patients, 53% (102) were women; the mean age was 68 ± 9 years. Data were collected at baseline, 4 months, and 12 months. Twelve months of follow-up has been shown to be adequate in studies with PROMs. Patient expectations were measured using the validated Hospital for Special Surgery Knee Replacement Expectation Survey on a scale from 0 to 100, with higher scores indicating higher expectations. We also assessed patient satisfaction, the Knee injury and Osteoarthritis Outcome Score, Forgotten Joint Score, High-Activity Arthroplasty Score, EQ-5D-3L, and the objective Knee Society Score. Bivariate linear correlations were analyzed using the Pearson or Spearman test. RESULTS: Preoperative patient expectations did not correlate with postoperative satisfaction. The mean Hospital for Special Surgery Knee Replacement Expectation Survey score was 82 ±16 points and did not correlate with satisfaction at either 4 months (r = -0.061; p = 0.42) or 12 months (r = -0.126; p = 0.11). Expectations did not correlate with patient characteristics or any of the preoperative or postoperative PROMs or the Knee Society Score. Patient satisfaction was 88% (158 of 179) at 4 months and 83% (160 of 193) at 12 months and did not correlate with patient characteristics or any of the preoperative PROMs or Knee Society Score. Patient satisfaction was medium to strongly correlated with postoperative PROMs and Knee Society Score. The Hospital for Special Surgery Knee Replacement Expectation Survey items with the most frequent expected improvement were "ability to walk" (99% [192 of 193]), "go downstairs" (99% [191 of 192]), and "go upstairs" (99% [192 of 193]). CONCLUSION: Preoperative expectations were not correlated with postoperative satisfaction or PROMs. Surgeons should be aware that patients have high expectations. However, these expectations appear to be less relevant in determining postoperative satisfaction. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparison of Responsiveness of Patient-Reported Outcome Measures After Total Knee Arthroplasty.

BACKGROUND: The aim of this study was to evaluate the responsiveness of different patient-reported outcome measures in patients with primary total knee arthroplasty (TKA). METHODS: In this prospective observational study, we assessed patients with TKA before the surgery, after 4 months, after 1 year, and after 2 years. Measures were the objective Knee Society Score (KSS) and the following patient-reported outcome measures: Knee injury and Osteoarthritis Outcome Score (KOOS), KOOS-12, Forgotten Joint Score (FJS-12), High-Activity Arthroplasty Score, and EQ-5D-3L. Responsiveness was determined by effect size (ES), standardized response mean (SRM), area under the receiver operating characteristics curve, floor and ceiling effects, and hypothesis testing. RESULTS: We analyzed data from 309 TKAs (272 patients, 56% female). The ES and SRM for the change in KSS, KOOS, KOOS-12, FJS-12, and EQ-5D-3L from baseline to each follow-up were large (>0.8). The largest responsiveness from baseline to follow-up was found for the KSS, KOOS/KOOS-12 quality of life, KOOS-12 summary, KOOS-12 pain, and FJS-12 (2.0 > ES <3.9, 1.4 > SRM <2.4). The area under the curve from baseline to each follow-up was ≥0.7 for KOOS, KOOS-12, and FJS-12 (range 0.71 to 0.95) and <0.7 for KSS and EQ-5D-3L (range 0.65 to 0.74). We found floor or ceiling effects in the KOOS, KOOS-12, and EQ-5D-3L, but not in the KSS, FJS-12, and High-Activity Arthroplasty Score. CONCLUSIONS: Our study demonstrated that responsiveness differed between the various measures. The KOOS-12 and FJS-12 showed the greatest internal and external responsiveness, although ceiling effects occurred in the KOOS-12.

Satisfaction after total knee arthroplasty: a prospective matched-pair analysis of patients with customised individually made and off-the-shelf implants.

PURPOSE: Customised individually made (CIM) total knee arthroplasty (TKA) was introduced to potentially improve patient satisfaction and other patient-reported outcome measures (PROMs). The purpose of this study was to compare PROMs, especially patient satisfaction, of patients with CIM and OTS TKA in a matched-pair analysis with a 2-year follow-up. METHODS: This is a prospective cohort study with a propensity score matching of 85 CIM and 85 off-the-shelf (OTS) TKA. Follow-up was at 4 months, 1 year and 2 years. The primary outcome was patient satisfaction. Secondary outcomes were as follows: overall improvement, willingness to undergo the surgery again, Knee injury and Osteoarthritis Outcome Score (KOOS), Forgotten Joint Score (FJS-12), High-Activity Arthroplasty Score (HAAS), EQ-5D-3L, EQ-VAS, Knee Society Score (KSS) and surgeon satisfaction. RESULTS: Patient satisfaction ranged from 86 to 90% and did not differ between CIM and OTS TKA. The EQ-VAS after 4 months and the HAAS after 1 year and 2 years were higher for CIM TKA. KOOS, FJS-12 and EQ-5D-3L were not different at follow-up. The changes in KOOS symptoms, pain and daily living were higher for OTS TKA. The KSS was higher for patients with CIM TKA. Surgeon satisfaction was high throughout both groups. Patients who were satisfied after 2 years did not differ preoperatively from those who were not satisfied. Postoperatively, all PROMs were better for satisfied patients. Patient satisfaction was not correlated with patient characteristics, implant or preoperative PROMs, and medium to strongly correlated with postoperative PROMs. CONCLUSION: Patient satisfaction was high with no differences between patients with CIM and OTS TKA. Both implant systems improved function, pain and health-related quality of life. Patients with CIM TKA showed superior results in demanding activities as measured by the HAAS. LEVEL OF EVIDENCE: II, prospective cohort study.

No difference in patient-reported satisfaction after 12 months between customised individually made and off-the-shelf total knee arthroplasty.

PURPOSE: A subset of patients is usually not satisfied after a total knee arthroplasty (TKA). Customised individually made (CIM) TKA are deemed to overcome drawbacks of classical off-the-shelf (OTS) TKA, but evidence is still sparse. The aim of this study was to compare satisfaction of patients with CIM and OTS TKA. METHODS: This prospective cohort study compared clinical and patient-reported outcome measures (PROM) between patients with CIM and OTS TKA. The primary outcome was patient satisfaction after 12 months. Secondary outcomes were the Knee Society Score (KSS), the Knee injury and Osteoarthritis Outcome Score (KOOS), the Forgotten Joint Score (FJS-12) and the EQ-5D-3L after 4 and 12 months. RESULTS: Data were analysed from 74 CIM TKA and 169 OTS TKA between January 2017 and September 2020. Patients with CIM TKA were slightly younger, more often male, had a lower body mass index, a lower KSS and partially higher preoperative PROMs. Patient satisfaction after 12 months was high and comparable (CIM 87%, OTS 89%). All PROMs improved for both groups (p < 0.001) and did not differ after 12 months (p > 0.063). The majority of patients improved above the minimal important difference (range 65 to 89%) and reported a clear overall improvement (CIM 86%, OTS 87%). The postoperative KSS, notably regarding knee stability, was higher for CIM TKA (p < 0.001). CONCLUSION: No difference was found in patient satisfaction between CIM and OTS TKA after 12 months. In both groups, patient satisfaction was high and PROMs improved considerably. LEVEL OF EVIDENCE: II, prospective cohort study.

From lin-benzoguanines to lin-benzohypoxanthines as ligands for Zymomonas mobilis tRNA-guanine transglycosylase: replacement of protein-ligand hydrogen bonding by importing water clusters.

The foodborne illness shigellosis is caused by Shigella bacteria that secrete the highly cytotoxic Shiga toxin, which is also formed by the closely related enterohemorrhagic Escherichia coli (EHEC). It has been shown that tRNA-guanine transglycosylase (TGT) is essential for the pathogenicity of Shigella flexneri. Herein, the molecular recognition properties of a guanine binding pocket in Zymomonas mobilis TGT are investigated with a series of lin-benzohypoxanthine- and lin-benzoguanine-based inhibitors that bear substituents to occupy either the ribose-33 or the ribose-34 pocket. The three inhibitor scaffolds differ by the substituent at C(6) being H, NH(2), or NH-alkyl. These differences lead to major changes in the inhibition constants, pK(a) values, and binding modes. Compared to the lin-benzoguanines, with an exocyclic NH(2) at C(6), the lin-benzohypoxanthines without an exocyclic NH(2) group have a weaker affinity as several ionic protein-ligand hydrogen bonds are lost. X-ray cocrystal structure analysis reveals that a new water cluster is imported into the space vacated by the lacking NH(2) group and by a conformational shift of the side chain of catalytic Asp102. In the presence of an N-alkyl group at C(6) in lin-benzoguanine ligands, this water cluster is largely maintained but replacement of one of the water molecules in the cluster leads to a substantial loss in binding affinity. This study provides new insight into the role of water clusters at enzyme active sites and their challenging substitution by ligand parts, a topic of general interest in contemporary structure-based drug design.

Localization of ubiquinone-8 in the Na+-pumping NADH:quinone oxidoreductase from Vibrio cholerae.

Na(+) is the second major coupling ion at membranes after protons, and many pathogenic bacteria use the sodium-motive force to their advantage. A prominent example is Vibrio cholerae, which relies on the Na(+)-pumping NADH:quinone oxidoreductase (Na(+)-NQR) as the first complex in its respiratory chain. The Na(+)-NQR is a multisubunit, membrane-embedded NADH dehydrogenase that oxidizes NADH and reduces quinone to quinol. Existing models describing redox-driven Na(+) translocation by the Na(+)-NQR are based on the assumption that the pump contains four flavins and one FeS cluster. Here we show that the large, peripheral NqrA subunit of the Na(+)-NQR binds one molecule of ubiquinone-8. Investigations of the dynamic interaction of NqrA with quinones by surface plasmon resonance and saturation transfer difference NMR reveal a high affinity, which is determined by the methoxy groups at the C-2 and C-3 positions of the quinone headgroup. Using photoactivatable quinone derivatives, it is demonstrated that ubiquinone-8 bound to NqrA occupies a functional site. A novel scheme of electron transfer in Na(+)-NQR is proposed that is initiated by NADH oxidation on subunit NqrF and leads to quinol formation on subunit NqrA.

Crystallization of the Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae.

The Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae couples the exergonic oxidation of NADH by membrane-bound quinone to Na+ translocation across the membrane. Na+-NQR consists of six different subunits (NqrA-NqrF) and contains a [2Fe-2S] cluster, a noncovalently bound FAD, a noncovalently bound riboflavin, two covalently bound FMNs and potentially Q8 as cofactors. Initial crystallization of the entire Na+-NQR complex was achieved by the sitting-drop method using a nanolitre dispenser. Optimization of the crystallization conditions yielded flat yellow-coloured crystals with dimensions of up to 200×80×20 µm. The crystals diffracted to 4.0 Šresolution and belonged to space group P2(1), with unit-cell parameters a=94, b=146, c=105 Å, α=γ=90, ß=111°.