Background:
Surgeons often prefer to use a tourniquet during minor procedures, such as carpal tunnel release (CTR) or trigger finger release (TFR). Besides the possible discomfort for the patient, ...the effect of tourniquet use on long-term results and complications is unknown. Our primary aim was to compare the patient-reported outcomes 1 year after CTR or TFR under local anesthesia with or without tourniquet. Secondary outcomes included satisfaction, sonographically estimated scar tissue thickness after CTR‚ and postoperative complications.
Methods:
Between May 2019 and May 2020, 163 patients planned for open CTR or TFR under local anesthesia were included. Before surgery, and at 3, 6, and 12 months postoperatively, Quick Disabilities of the Arm, Shoulder and Hand and Boston Carpal Tunnel questionnaires were administered, and complications were noted. At 6 months postoperatively, an ultrasound was conducted to determine the thickness of scar tissue in the region of median nerve.
Results:
A total of 142 patients (51 men 38%) were included. The Quick Disabilities of the Arm, Shoulder and Hand questionnaire and Boston Carpal Tunnel Questionnaire scores improved significantly in both groups during follow-up, wherein most improvements were seen in the first 3 months. No difference in clinical outcome and scar tissue formation was found between the two groups after 12 months. The complication rate was comparable between both groups. Thirty-two (24%) patients had at least one complication, none needed surgical interventions, and no recurrent symptoms were seen.
Conclusions:
Our study shows similar long-term clinical outcomes, formation of scar tissue, and complication rates for patients undergoing CTR or TFR with or without a tourniquet. Tourniquet usage should be based on shared decision-making.
Background:
The time until return to work (RTW) and possible factors affecting this time after proximal interphalangeal (PIP) joint arthroplasty are unknown. Therefore, we aim to evaluate the RTW ...after PIP joint arthroplasty for osteoarthritis and assess factors affecting the time until return to their usual work.
Methods:
We used prospectively gathered data from 74 patients undergoing PIP joint arthroplasty with daily hand surgery practice routine outcome collection. Standardized RTW questionnaires were completed at 6 weeks and 3, 6, and 12 months after surgery. Return to work was defined as the first time a patient reported returning to work and performing the original work for a minimum of 50% of the original hours a week, as stated in the patient’s contract. Second, we evaluated baseline factors affecting the time until RTW.
Results:
The probability of RTW within 12 months after surgery was 88%. The median time until RTW was 8 weeks (interquartile range: 4-10). Physical occupational intensity (hazard ratio HR: 0.36, P = .001) and the baseline Michigan Hand Outcomes Questionnaire work scores (HR: 1.02, P = .005) were independently associated with RTW.
Conclusion:
In conclusion, patients returned to work after a median of 8 weeks following PIP arthroplasty. Patients with medium or heavy physical occupations returned to work later than patients with light physical occupations. Better patient-reported work outcomes at baseline also led to an earlier RTW. This information can be valuable for providing adequate information during the preoperative consultation.
An increasing number of genes are being described in the context of non-syndromic male infertility. Linking the underlying genetic causes of non-syndromic male infertility with clinical data from ...patients is important to establish new genotype-phenotype correlations. This process can be facilitated by using universal nomenclature, but no standardized vocabulary is available in the field of non-syndromic male infertility. The International Male Infertility Genomics Consortium aimed at filling this gap, providing a standardized vocabulary containing nomenclature based on the Human Phenotype Ontology (HPO). The "HPO tree" was substantially revised compared with the previous version and is based on the clinical work-up of infertile men, including physical examination and hormonal assessment. Some causes of male infertility can already be suspected based on the patient's clinical history, whereas in other instances, a testicular biopsy is needed for diagnosis. We assembled 49 HPO terms that are linked in a logical hierarchy and showed examples of morphological features of spermatozoa and testicular histology of infertile men with identified genetic diagnoses to describe the phenotypes. This work will help to record patients' phenotypes systematically and facilitate communication between geneticists and andrologists. Collaboration across institutions will improve the identification of patients with the same phenotypes, which will promote the discovery of novel genetic causes for non-syndromic male infertility.
Background/Introduction:
In this study, we wanted to compare the pyrocarbon disc interposition arthroplasty (PDI) with trapeziectomy plus ligament reconstruction tendon interposition (LRTI). ...Primarily, we tested whether PDI resulted in a higher pinch strength. Secondarily, we compared the grip strength, range of motion (ROM), patient reported outcomes, satisfaction and complications.
Methods:
Due to scarcity of preoperative hand measurements, we performed a descriptional cross-sectional cohort study of patients operated between 2006 and 2014, with a minimum of 5 years of follow-up. Patients were treated with PDI or LRTI. We determined key pinch strength as primary outcome, followed by tip- and tripod pinch, grip strength, palmar abduction and opposition; the Michigan Hand Outcome Questionnaire (MHQ), Patient Reported hand and Wrist evaluation (PRWHE), satisfaction and complications. Propensity score matching was used to match both study groups on demographic variables. A ratio of 2:1 was used resulting in inclusion of 62 (of 154) PDI and 31 (of 31) LRTI thumbs.
Results:
The PDI-group patients showed stronger key and tip pinch strength than the LRTI group (p=0.027 and p=0.036 respectively). Tripod pinch, grip strength and ROM were equal for both groups. MHQ and PRWHE were comparable, with higher satisfaction for the PDI group. Eight PDI patients were converted to LRTI due to pain.
Conclusion/discussion:
This study confirmed our hypothesis that key and tip pinch strength is stronger after PDI compared to LRTI for CMC-1 joint osteoarthritis. Both techniques have comparable outcomes considering patient reported outcome (MHQ and PRWHE), ROM and complications.
Aims
The primary aim of this study was to describe long-term patient-reported outcomes after ulna shortening osteotomy for ulna impaction syndrome.
Methods
Overall, 89 patients treated between July ...2011 and November 2017 who had previously taken part in a routine outcome evaluation up to 12 months postoperatively were sent an additional questionnaire in February 2021. The primary outcome was the Patient-Rated Wrist and Hand Evaluation (PRWHE) total score. Secondary outcomes included patient satisfaction with treatment results, complications, and subsequent treatment for ulnar-sided wrist pain. Linear mixed models were used to compare preoperative, 12 months, and late follow-up (ranging from four to nine years) PRWHE scores.
Results
Long-term outcomes were available in 66 patients (74%) after a mean follow-up of six years (SD 1). The mean PRWHE total score improved from 63 before surgery to 19 at late follow-up (difference in means (Δ) 44; 95% confidence interval (CI) 39 to 50; p = <0.001). Between 12 months and late follow-up, the PRWHE total score also improved (Δ 12; 95% CI 6 to 18; p = < 0.001). At late follow-up, 14/66 of patients (21%) reported a PRWHE total score of zero, whereas this was 3/51 patients (6%) at 12 months (p = 0.039). In all, 58/66 patients (88%) would undergo the same treatment again under similar circumstances. Subsequent treatment (total n = 66; surgical n = 57) for complications or recurrent symptoms were performed in 50/66 patients (76%). The most prevalent type of reoperation was hardware removal in 42/66 (64%), and nonunion occurred in 8/66 (12%).
Conclusion
Ulna shortening osteotomy improves patient-reported pain and function that seems to sustain at late follow-up. While satisfaction levels are generally high, reoperations such as hardware removal are common. Cite this article: Bone Jt Open 2022;3(5):375–382.
There is a critical need for more-effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing ...clinical drugs to be repurposed as antibiotics. We examined the mechanisms of action and basis of innate Gram-negative resistance for the anthelmintic drug niclosamide and subsequently exploited this information to demonstrate that niclosamide and analogs kill Gram-negative bacteria when combined with antibiotics that inhibit drug efflux or permeabilize membranes. We confirm the synergistic potential of niclosamide
in vitro
against a diverse range of recalcitrant Gram-negative clinical isolates and
in vivo
in a mouse abscess model. We also demonstrate that nitroreductases can confer resistance to niclosamide but show that evolution of these enzymes for enhanced niclosamide resistance confers a collateral sensitivity to other clinical antibiotics. Our results highlight how detailed mechanistic understanding can accelerate the evaluation and implementation of new combination therapies.
ABSTRACT
One avenue to combat multidrug-resistant Gram-negative bacteria is the coadministration of multiple drugs (combination therapy), which can be particularly promising if drugs synergize. The identification of synergistic drug combinations, however, is challenging. Detailed understanding of antibiotic mechanisms can address this issue by facilitating the rational design of improved combination therapies. Here, using diverse biochemical and genetic assays, we examine the molecular mechanisms of niclosamide, a clinically approved salicylanilide compound, and demonstrate its potential for Gram-negative combination therapies. We discovered that Gram-negative bacteria possess two innate resistance mechanisms that reduce their niclosamide susceptibility: a primary mechanism mediated by multidrug efflux pumps and a secondary mechanism of nitroreduction. When efflux was compromised, niclosamide became a potent antibiotic, dissipating the proton motive force (PMF), increasing oxidative stress, and reducing ATP production to cause cell death. These insights guided the identification of diverse compounds that synergized with salicylanilides when coadministered (efflux inhibitors, membrane permeabilizers, and antibiotics that are expelled by PMF-dependent efflux), thus suggesting that salicylanilide compounds may have broad utility in combination therapies. We validate these findings
in vivo
using a murine abscess model, where we show that niclosamide synergizes with the membrane permeabilizing antibiotic colistin against high-density infections of multidrug-resistant Gram-negative clinical isolates. We further demonstrate that enhanced nitroreductase activity is a potential route to adaptive niclosamide resistance but show that this causes collateral susceptibility to clinical nitro-prodrug antibiotics. Thus, we highlight how mechanistic understanding of mode of action, innate/adaptive resistance, and synergy can rationally guide the discovery, development, and stewardship of novel combination therapies.
IMPORTANCE
There is a critical need for more-effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing clinical drugs to be repurposed as antibiotics. We examined the mechanisms of action and basis of innate Gram-negative resistance for the anthelmintic drug niclosamide and subsequently exploited this information to demonstrate that niclosamide and analogs kill Gram-negative bacteria when combined with antibiotics that inhibit drug efflux or permeabilize membranes. We confirm the synergistic potential of niclosamide
in vitro
against a diverse range of recalcitrant Gram-negative clinical isolates and
in vivo
in a mouse abscess model. We also demonstrate that nitroreductases can confer resistance to niclosamide but show that evolution of these enzymes for enhanced niclosamide resistance confers a collateral sensitivity to other clinical antibiotics. Our results highlight how detailed mechanistic understanding can accelerate the evaluation and implementation of new combination therapies.
Infertility affects around 7% of the male population and can be due to severe spermatogenic failure (SPGF), resulting in no or very few sperm in the ejaculate. We initially identified a homozygous ...frameshift variant in FKBP6 in a man with extreme oligozoospermia. Subsequently, we screened a total of 2,699 men with SPGF and detected rare bi-allelic loss-of-function variants in FKBP6 in five additional persons. All six individuals had no or extremely few sperm in the ejaculate, which were not suitable for medically assisted reproduction. Evaluation of testicular tissue revealed an arrest at the stage of round spermatids. Lack of FKBP6 expression in the testis was confirmed by RT-qPCR and immunofluorescence staining. In mice, Fkbp6 is essential for spermatogenesis and has been described as being involved in piRNA biogenesis and formation of the synaptonemal complex (SC). We did not detect FKBP6 as part of the SC in normal human spermatocytes, but small RNA sequencing revealed that loss of FKBP6 severely impacted piRNA levels, supporting a role for FKBP6 in piRNA biogenesis in humans. In contrast to findings in piRNA-pathway mouse models, we did not detect an increase in LINE-1 expression in men with pathogenic FKBP6 variants. Based on our findings, FKBP6 reaches a “strong” level of evidence for being associated with male infertility according to the ClinGen criteria, making it directly applicable for clinical diagnostics. This will improve patient care by providing a causal diagnosis and will help to predict chances for successful surgical sperm retrieval.
Display omitted
Bi-allelic loss-of-function variants in FKBP6 cause human male infertility due to round spermatid arrest. Absence of this piRNA factor leads to a reduction of pachytene piRNAs, which likely disrupts piRNA-mediated translational regulation in germ cells from mid-meiosis on. In contrast to many piRNA-factor mouse models, LINE-1 overexpression is not observed.
Background:
Pulmonary edema and left ventricular thrombosis may arise during veno-arterial extracorporeal life support due to an increase in cardiac load. This mechanical stress can be reduced ...through different left ventricular unloading techniques. We set out to quantitatively summarize the hemodynamic effects of available methods in patients treated with veno-arterial extracorporeal life support.
Methods:
Literature was systematically searched for studies reporting left ventricular unloading during veno-arterial extracorporeal life support as reflected by changes in left atrial pressure, pulmonary capillary wedge pressure, diastolic pulmonary artery pressure, or left ventricular end-diastolic pressure. For studies including ⩾10 patients per group, changes in these parameters were pooled using (1) standardized mean differences and (2) ratio of means. Assessment of potential bias was performed for all studies.
Results:
Eight studies met the inclusion criteria. Reported techniques included use of intra-aortic balloon pump (n = 1), micro-axial blood pump (Impella®, n = 2), left ventricular venting (n = 1), and atrial septostomy (n = 4). Overall, left ventricular unloading was associated with a statistically significant reduction in preload parameters (standardized mean differences = −1.05 (95% confidence interval = −1.24 to −0.86) and ratio of means = 0.60 (0.47 to 0.76)). Effect sizes were strongest for micro-axial blood pump and atrial septostomy (standardized mean differences = −1.11 (−1.55 to −0.68) and −1.22 (−1.47 to −0.96), and ratio of means = 0.58 (0.39 to 0.86) and 0.54 (0.36 to 0.83), respectively).
Conclusion:
Left ventricular unloading was associated with a significant reduction in left ventricular preload parameters in the setting of veno-arterial extracorporeal life support. This effect may be most pronounced for micro-axial blood pump and atrial septostomy.
CKD and ICD Related Complications
Introduction
Implantable cardioverter defibrillator (ICD) implantation has become an accepted therapy for the prevention of sudden cardiac death. However, serious ...comorbidities such as chronic kidney disease (CKD) are influencing the beneficial effects of ICD therapy. In this study, the association between kidney function and the occurrence of ICD related complications was assessed.
Methods
All patients receiving an ICD or cardiac resynchronization therapy‐defibrillator between 1996 and 2012 were included. Renal function was categorized as: glomerular filtration rate (GFR) >90, GFR 30–90 or GFR <30 mL/min/1.73 m2. Registered complications were pocket hematoma, pneumothorax, lead complications, and device infection.
Results
In 3,147 device recipients, 236 patients (7.5%) suffered from at least 1 complication. Patients with a GFR <30 (n = 110) had a higher event rate for hematoma, pneumothorax, and infection. These patients were older, had a higher incidence of hypertension, diabetes, and a lower body mass index (BMI; P < 0.05). After correcting for these risk factors, hematoma remained independently associated with a GFR <30 mL/min (OR 2.7, CI: 1.05–6.9, P = 0.04). Device infection, pneumothorax, and lead complications were not independently associated with a GFR <30 mL/min/1.73 m2.
Conclusions
Patients with CKD suffered from more ICD related complications than patients without kidney disease. This was partially associated with kidney dysfunction itself as was the case with the occurrence of hematoma. However, the high burden of risk factors associated with device complications in patients with renal disease played an important role as well.
The primary aim of this study was to analyze the median time until patients performed their usual work following an ulnar shortening osteotomy (USO). The secondary aim was to identify factors ...influencing the median time until return to their usual work.
We used a retrospective cohort of patients with ongoing data collection from our institution in the Netherlands. Patients with paid employment who underwent USO were invited to complete a return-to-work questionnaire at 6 weeks, 3 months, 6 months, and 12 months after surgery. The probability of and median time until return to usual work were assessed using an inverted Kaplan-Meier analysis. Factors influencing the return to usual work were evaluated using multivariable Cox proportional hazard regression.
In total, 111 patients who underwent USO were included, with a mean age of 46 years. The probability of returning to usual work in the first year was 92%, and the median time was 12 weeks. The type of work was independently associated with a return to work, with median times of 8, 12, and 14 weeks for light, moderate, and heavy physical work, respectively. We did not find differences in return to usual work based on age, sex, duration of complaints until surgery, treatment side, smoking status, the preoperative Patient-Rated Wrist Evaluation score, or whether the osteotomy was performed freehand or with an external cutting device.
Half of the patients that underwent USO fully performed their usual work by 12 weeks following surgery. We found that 92% of the patients performed their usual work within 1 year after surgery. We found a large variation in the time until a return to work based on the type of work. Surgeons can use this data to inform patients on the rehabilitation phase after USO.
Prognostic IV.
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