Effect of the oxytocin receptor antagonist nolasiban on pregnancy rates in women undergoing embryo transfer following IVF: analysis of three randomised clinical trials.

STUDY QUESTION: Does a single oral dose of nolasiban 900 mg administered 4 h before embryo transfer (ET) increase pregnancy rates in women undergoing IVF? SUMMARY ANSWER: In an individual patient data (IPD) meta-analysis of three clinical trials, a single oral dose of nolasiban 900 mg was associated with an increased ongoing pregnancy rate of an absolute 5% (relative 15%). WHAT IS KNOWN ALREADY: Several clinical studies have shown that blocking activation of oxytocin receptors by an oxytocin receptor (OTR) antagonist has the potential to decrease uterine contractions, increase endometrial perfusion and enhance endometrial decidualisation and other parameters of endometrial receptivity. It has been hypothesised that antagonism of oxytocin receptors could improve the likelihood of successful embryo implantation and thus increase pregnancy and live birth rates following ET. STUDY DESIGN, SIZE, DURATION: This is an analysis of three randomised, double-blind, placebo-controlled trials, which randomised 1836 subjects between 2015 and 2019. We describe the results of a meta-analysis of individual participant data (IPD) from all three trials and the pre-specified analyses of each individual trial. PARTICIPANT/MATERIAL, SETTING, METHODS: Participants were patients undergoing ET following IVF/ICSI in 60 fertility centres in 11 European countries. Study subjects were below 38 years old and had no more than one previously failed cycle. They were randomised to a single oral dose of nolasiban 900 mg (n = 846) or placebo (n = 864). In IMPLANT 1, additional participants were also randomised to nolasiban 100 mg (n = 62) or 300 mg (n = 60). Fresh ET of one good quality embryo (except in IMPLANT 1 where transfer of two embryos was allowed) was performed on Day 3 or Day 5 after oocyte retrieval, approximately 4 h after receiving the study treatment. Serum hCG levels were collected at 14 days post oocyte retrieval (Week 2) and for women with a positive hCG result, ultrasound was performed at Week 6 post-ET (clinical pregnancy) and at Week 10 post-ET (ongoing pregnancy). Pregnant patients were followed for maternal (adverse events), obstetric (live birth, gestational age at delivery, type of delivery, incidence of twins) and neonatal (sex, weight, height, head circumference, Apgar scores, congenital anomalies, breast feeding, admission to intensive care and specific morbidities e.g. jaundice, respiratory distress syndrome) outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: In an IPD meta-analysis of the clinical trials, a single oral dose of nolasiban 900 mg was associated with an absolute increase of 5.0% (95% CI 0.5, 9.6) in ongoing pregnancy rate and a corresponding increase of 4.4% (95% CI -0.10, 8.93) in live birth rate compared to placebo. Similar magnitude increases were observed for D3 or D5 transfers but were not significantly different from the placebo. Population pharmacokinetics (PK) demonstrated a correlation between higher exposures and pregnancy. LIMITATIONS, REASON FOR CAUTION: The meta-analysis was not a pre-specified analysis. While the individual trials did not show a consistent significant effect, they were not powered based on an absolute increase of 5% in ongoing pregnancy rate. Only a single dose of up to 900 mg nolasiban was administered in the clinical trials; higher doses or extended regimens have not been tested. Only fresh ET has been assessed in the clinical trials to date. WIDER IMPLICATIONS OF THE FINDINGS: The finding support the hypothesis that oxytocin receptor antagonism at the time of ET can increase pregnancy rates following IVF. The overall clinical and population PK data support future evaluation of higher doses and/or alternate regimens of nolasiban in women undergoing ET following IVF. STUDY FUNDING/COMPETING INTERESTS: The trials were designed, conducted and funded by ObsEva SA. A.H., O.P., E.G., E.L. are employees and stockholders of ObsEva SA. E.L. is a board member of ObsEva SA. G.G. reports honoraria and/or non-financial support from ObsEva, Merck, MSD, Ferring, Abbott, Gedeon-Richter, Theramex, Guerbet, Finox, Biosilu, Preglem and ReprodWissen GmbH. C.B. reports grants and honoraria from ObsEva, Ferring, Abbott, Gedeon Richter and MSD. P.P. reports consulting fees from ObsEva. H.T. reports grants and or fees from ObsEva, Research Fund of Flanders, Cook, MSD, Roche, Gedeon Richter, Abbott, Theramex and Ferring. H.V. reports grants from ObsEva and non-financial support from Ferring. P.T. is an employee of Cytel Inc., who provides statistical services to ObsEva. J.D. reports consulting fees and other payments from ObsEva and, Scientific Advisory Board membership of ObsEva. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02310802, NCT03081208, NCT03758885. TRIAL REGISTRATION DATES: December 2014 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885). FIRST PATIENT'S ENROLMENT: January 2015 (NCT02310802), March 2017 (NCT03081208), November 2018 (NCT03758885).

Individualized vaginal bleeding experience of women with uterine fibroids in the PEARL I randomized controlled trial comparing the effects of ulipristal acetate or placebo.

RESEARCH QUESTION: What is the individualized bleeding experience of women with fibroids and anaemia in a 3 month randomized placebo controlled trial (PEARL I) of the selective progesterone receptor modulator (SPRM), ulipristal acetate (UPA)? SUMMARY ANSWER: In contrast to continuing excessive regular menstruation in the placebo group, a majority of women treated with UPA (63.1% of those on 5 mg/day and 71.3% of those on 10 mg/day) experienced the rapid onset of amenorrhoea or minimal blood loss [pictorial blood loss assessment chart (PBAC) < 12]. The remainder experienced various patterns of bleeding and intensity of blood loss that are described for the first time, including an association of irregular bleeding on UPA with sub-mucous fibroids. WHAT IS KNOWN ALREADY: The majority experience on UPA is amenorrhoea but the bleeding experience of the others has not been characterized. STUDY DESIGN, SIZE, DURATION: A 13 week randomized controlled trial in women, eligible for surgery for uterine fibroids and anaemia, comparing placebo (n = 48), UPA 5 mg (n = 95) or UPA 10 mg (n = 94). The treatment aim was fibroid shrinkage and the primary definitions and outcomes are published elsewhere; here the secondary outcome measure of vaginal bleeding pattern is described. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women, 18-50 years old, with fibroids and haemoglobin ≤10.2 g/dl, justifying surgery. At least one fibroid was 3-10 cm diameter and uterus ≤16 weeks pregnancy size. All used the daily PBAC methodology in a screening cycle (Ps) and throughout treatment, and for the 4 weeks preceding Week 26 and Week 38 in those who did not have surgery. An excessive menstruation is PBAC > 100. The bleeding patterns were characterized using the classification of Belsey, developed under auspices of WHO. MAIN RESULTS AND THE ROLE OF CHANCE: In the placebo group, all women had an excessive screening PBAC [median 376; interquartile range (IQR) 241-574]; 81.3% of them had regular menstrual bleeding and the intensity of bleeding remained similar, so that the median PBAC in the next three periods was 90, 92 and 93% of the screening value. Four of the 48 women had spontaneous improvement in bleeding and one developed amenorrhoea and elevation of gonadotrophins. In the placebo group, 22 women provided Week 26 and 21 women provided Week 38 PBAC data. The median Week 26 PBAC (312: IQR 102-524) and Week 38 PBAC (236; IQR 103-465) indicated ongoing excessive bleeding. In the UPA group, screening PBAC confirmed excessive bleeding (UPA 5 mg, median 358; IQR 232-621; UPA 10 mg, median 330; IQR 235-542). UPA was initiated from the start of a menstruation (P1) and no women had regular periods on treatment. Following P1 through the whole of the remaining 13 weeks of UPA treatment amenorrhoea or minimal loss (PBAC < 12 for whole phase) occurred in 63.1% (UPA 5 mg) or 71.3% (UPA 10 mg). The characterization of the individualized bleeding experience of the remaining women on 5 mg and 10 mg UPA, respectively, were infrequent bleeding in 17.9 and 12.8%; frequent or prolonged bleeding or both in 12.7 and 11.7% and irregular bleeding in 5.3 and 3.2%. In those with prolonged, frequent or irregular bleeding there was a high chance that sub-mucous fibroids were present (UPA 5 mg 100% and UPA 10 mg 78.6%) but no correlation with progesterone receptor modulator-associated endometrial changes. LIMITATIONS, REASONS FOR CAUTION: The follow-up PBAC data at Week 26 and Week 38 are only valid for women who did not have surgical intervention. These groups may not be representative of the groups at screening. WIDER IMPLICATIONS OF THE FINDINGS: This first detailed description of these SPRM bleeding patterns provides clinicians with an indication of potential responses in women using the SPRM UPA and provides an extended definition of bleeding in untreated women with excessive bleeding and fibroids. STUDY FUNDING/COMPETING INTEREST(S): Funded by PregLem/Gedeon Richter. D.H.B. is a member of the Scientific Advisory Board of PregLem, and in this role participated in the study design and supervision. Stock originally held in PregLem was given up when PregLem was incorporated into Gedeon Richter; D.H.B. does not currently hold stock. M.A.L. has received payment from Gideon Richter to attend a meeting to present these data (Barcelona, April 2013) but no financial support in preparing the manuscript. B.C.J.M.F. is a member of the Scientific Advisory Board of PregLem and has received fees and grant support from the following companies: Andromed, Ardana, Auxogyn, Ferring, Genovum, Gedeon Richter, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Roche, Schering, Schering Plough, Serono, Watson Laboratories and Wyeth. P.T. is a paid statistical consultant for PregLem SA. E.B. is a full time employee of PregLem and received payment from stocks sold in October 2010 from the company's full acquisition by Gedeon Richter Group. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT00755755 (PEARL I).

Muscle Belly Repair: Biomechanical Assessment of the Anchor Suture and the Modified Kessler Techniques.

Background: Treatment of muscle belly lacerations remains a problem for surgeons. Inadequate repair of lacerations can cause functional disability. To date, there is no consensus on the method of repair for these injuries. We have previously described a technique of repairing mid-substance muscle belly lacerations. The aim of this study was to determine the ultimate strength of an intact muscle belly and to compare the anchor suture (AS) technique with the modified Kessler (MK) technique. Methods: Fifteen fresh frozen hind-legs from adolescent pigs were divided into three groups and used for the testing. Each group consisted of five specimens. Group one was the intact control group, group two was repaired with the MK technique and group three was repaired with the AS technique. Following repair, the muscles were secured in a custom-made fixation apparatus and underwent linear tensioning at a rate of 25 mm/min, generating a load-displacement curve for each specimen. The data regarding ultimate strength, modes of failure and number of intact suture/anchor constructs (for groups 2 and 3) was calculated. Results: The ultimate strength of the intact muscle group of was found to be 608.1 ± 107.9  N. This was significantly (p < 0.05) higher than the pull-out strength of the MK and AS groups. The pull-out strength of the AS group was 143.1 ± 36.7 N, nearly twice that of the MK group 69.8 ± 16.4 N (p = 0.11). Suture pull-out was the most common mode of failure. Conclusions: The AS technique was found to have both higher strain and nearly twice the ultimate pull-out strength compared to the MK repair group. We suggest the AS technique as a viable technique for mid-substance muscle belly repairs.

Superior medial geniculate artery pseudoaneurysm after primary total knee arthroplasty.

Vascular complications after total knee arthroplasty are rare. To date, there are 7 reported cases of pseudoaneurysms affecting the popliteal artery and 6 cases affecting one of the geniculate arteries. We present a case of a geniculate artery pseudoaneurysm that shared symptoms of a deep venous thrombosis on physical examination of a patient who underwent primary total knee arthroplasty. To date, there are no reports in American literature of pseudoaneurysms affecting the superior medial geniculate artery after primary total knee arthroplasty. After a vascular workup including computed tomographic angiography, surgical management included evacuation of the pseudoaneurysm and ligation of the feeding artery. The patient went on to successful recovery.

Split-thickness skin graft donor sites: a comparative study of two absorbent dressings.

OBJECTIVE: To identify the optimal dressing for split-thickness skin graft (SSG) donor sites. METHOD: This prospective randomised controlled trial compared two dressings - a new absorbent form of a polyurethane film dressing (Tegaderm Absorbent, 3M) and our standard alginate dressing (Kaltostat, ConvaTec) - on SSG donor sites in 40 patients. Primary outcome measures were: reduced time to full healing; reduced postoperative pain; reduced leakage rates from the dressing. Secondary outcome measures related to acceptability of the dressings to the patient. RESULTS: On removal of the dressings at the first assessment, 79% of the Tegaderm Absorbent donor sites had healed completely, compared with 16% of the Kaltostat ones (p<0.001).A significantly greater median area had healed with Tegaderm Absorbent (100%), when compared with Kaltostat (89%) (p<0.001). Mean time to complete healing was also significantly faster for Tegaderm Absorbent than Kaltostat (14 versus 21 days) (p<0.001). Significantly fewer subjects experienced postoperative pain with Tegaderm Absorbent on both day 1 (21% versus 67%, p=0.006, NNT=3) and day 2 (17% versus 75%, p<0.001, NNT=2). Leakage rates reduced by 48% with Tegaderm Absorbent, with no leakage in the smaller donor sites. Tegaderm Absorbent was significantly easier to apply than Kaltostat (89% versus 27% found it'very easy') as was ease of removal (84% versus 11% found it'very easy') (p<0.0001). Patients found Tegaderm Absorbent dressings significantly more convenient to manage and bathe with. At one month post-surgery, Vancouver scar scores showed thatTegaderm Absorbent donor sites were less red, flatter, softer and less itchy. CONCLUSION: Tegaderm Absorbent provides a significant improvement in terms of donor-site pain, healing and ease of management.

The use of GORE-TEX bags for hand burns.

Clinical and laboratory studies were made to compare the water vapour permeability, bacteriological properties and clinical performance of polythene and polytetrafluoroethylene fabric (GORE-TEX) bags in the treatment of hand burns. Polythene bags are virtually impermeable to saline, whereas GORE-TEX bags containing silver sulphadiazine cream show a water vapour permeability of 0.53 ml/cm2/day, resulting in a 30 per cent weight reduction of added water after 48 h. Clinically, hand maceration and accumulation of exudate are significantly reduced in hands treated in GORE-TEX bags. The mean daily volume of accumulated exudate for GORE-TEX bags was 37 ml compared to 83 ml for polythene (P less than 0.01). When adjusted for the percentage area of the hand surface burned, this reduction remained significant (P less than 0.005). A tendency for less pain and better hand movement was noted with GORE-TEX bags. There were no significant differences in rate of healing or bacterial colonization of the burned hand between the two type of bags. GORE-TEX bags prevent skin maceration and accumulation of exudate, allowing ease of burn assessment and improved hand function. They are also durable and non-slip, thus increasing patient independence.

Ring avulsion injuries managed with homodigital and heterodigital Venous Island Conduit (VIC) flaps.

Ring avulsion injury frequently results in vascular insufficiency (venous or arterial) and soft tissue injury. We report four cases requiring revascularization where venous congestion and dorsal skin cover were achieved using a composite pedicled venous flow-through flap. We have termed this a Venous Island Conduit (VIC) Flap. Two types of flaps, homodigital and heterodigital, were used, depending on the severity of the injury. The techniques and results are discussed. Venous island conduit flaps are ideally suited to the management of ring avulsion injury and have several advantages over the alternatives.

A comparison of three primary non-adherent dressings applied to hand surgery wounds.

This study reports the results of a prospective randomised controlled trial that compared three non-adherent wound dressings applied to hand surgery wounds. Paraffin-impregnated gauze (Jelonet) was compared with a cellulose, acetate fibre dressing coated with a petrolatum emulsion (Adaptic) and a polyamide net dressing impregnated with silicone gel (Mepitel). The dressings were assessed for their ease of application and removal, pain on removal and wound appearance. Results from 99 patients were available for analysis. Adaptic was significantly easier to remove (p < 0.01), required less soaking (p < 0.05), was less painful to remove (p < 0.05) and caused less wound maceration (p < 0.05) than Jelonet, but was significantly more difficult to apply (p < 0.05). Mepitel was also easier to remove but this did not reach statistical significance. It was also more difficult to apply than Jelonet (p < 0.05). We recommend that Adaptic should be used routinely as the non-adherent dressing for incisions or traumatic wounds on the hand. The slight increased difficulty in applying the dressing is outweighed by the major advantages associated with its removal.

Assessing PTFE bags for the treatment of hand burns.

A report of a trial comparing the effectiveness of polythene and polytetrafluoroethylene hand bags in the treatment of burns.

Simplified and strong: abductor pollicus longus suspension arthroplasty with biotenodesis screw fixation in the base of the index metacarpal.

Surgical treatment of thumb basal joint arthritis is aimed at pain relief, restoration of pinch strength, and stability. We describe a variation of the abductor pollicus longus (APL) suspension arthroplasty originally described by Thompson, which maximizes strength of repair and is technically simple to perform. The technique consists of a trapeziectomy followed by resection of a slip of the APL and secure docking of the tendon into the base of the index metacarpal base. Stability is enhanced with a 3.0 mm biotenodesis screw. From March 2009 to September 2011, 50 patients were treated at our institution. Early results showed consistent pain relief, functional improvement, and minimal complications. The data support APL suspension arthroplasty with tenodesis screw fixation as a safe and effective treatment for CMC arthritis.

Anchor suture technique for muscle belly repair.

Upper extremity lacerations occur frequently. Although surgical indications for tendon repair are widely accepted, indications for repairing the midsubstance of muscles are not as clear. As the standard of care for muscle repair is absent, there are a variety of techniques available to the treating surgeon. In this study, we describe a technique used on several patients seen in our orthopedic practice. The use of orthogonally placed anchor sutures allows for more reliable suture passes and purchase in the muscle belly compared with simple end-to-end approximation. Furthermore, our technique does not introduce excessive foreign material as has been suggested by previous techniques.

Survival of porcine mesenchymal stem cells over the alginate recovered cellular method.

Although previous studies have established alginate as a three-dimensional scaffold for chondrogenic differentiation of mesenchymal stem cells (MSCs), little is known about the cytotoxic effects of the polymerizing and chelating reagents used in the alginate recovered cellular method. Swine MSCs (sMSC) were suspended in the polymerizing agent, CaCl(2), and viability was assessed using a trypan blue exclusion assay at intervals over 2 h. MSCs were also suspended in two different chelating agents, 55 mM sodium citrate and 50 mM EDTA, and viability was calculated. Finally, sMSCs and human MSCs were encapsulated and cultured in vitro. The sMSC were collected at day 4 and the cells were recovered by chelation. Encapsulated hMSCs were cultured with TGFß3 and IGF-1 and assayed by qRT-PCR for collagen types I and II and sox9 with encapsulated human dermal fibroblasts and chondrocytes as controls recovered on days 0, 7, and 14. Only 53% of sMSCs were viable after 10 min in CaCl(2), the standard polymerization period, whereas 94% of encapsulated sMSCs in polymerized alginate were alive at 15 days. After 20 min in chelating agents, sodium citrate and EDTA, only 46% and 17% of the cells, were viable, respectively. The alginate recovered sMSCs yielded 12% survival. Human MSCs upregulated cartilage-specific collagen type II over the 14-day culture. Collagen I remained unchanged in the hMSCs. Alginate is a suitable agent for chondrodifferentiation of MSCs and can be dissolved by chelation, but the agents involved in hydrogel polymerization and cell recovery should be altered to improve MSC survival.

Subchondral cysts of the atlantoaxial joint: a risk factor for odontoid fractures in the elderly.

BACKGROUND CONTEXT: Scholars have postulated that cervical degeneration can predispose the upper cervical spine to injury after minor trauma. Subchondral cysts have previously been recognized as potentiators of fracture in the hip and knee but no cases of cervical degenerative cysts contributing to fracture have been reported. PURPOSE: This report documents a case series in which patients sustained significant injury to the upper cervical spine in the setting of subchondral cervical cysts. STUDY DESIGN/SETTING: Case series/academic level I trauma center. METHODS: Between 2004 and 2008, six patients (ages 73-91 years) with cervical pathology were admitted to the trauma service at our Level I trauma center. The most common mechanism of injury was a low velocity fall, which occurred in 5 out of 6 patients. All patients suffered an odontoid fracture. In all cases, there was radiographic evidence of cyst formation, and computed tomographic imaging demonstrated fracture communication with the subchondral cyst. RESULTS: Of the six cases, four were treated definitively with immobilization in a cervical orthosis and two required surgery. One patient was treated with an occipital-cervical fusion, whereas the other underwent Brooks wiring. All patients ultimately went on to heal their fractures. CONCLUSIONS: Degenerative changes in the cervical spine have previously been recognized to potentiate injury. This report raises the question of whether degenerative processes at the C1-C2 articulation predispose elderly patients to injury at this level. The presence of cystic degeneration at the atlantoaxial joint should be recognized as a potential risk factor for cervical injury after relatively minor trauma.

Multidirectional instability of the shoulder in elite female gymnasts.

Multidirectional instability (MDI) of the shoulder is symptomatic laxity in 2 or more directions, 1 of which is inferior. MDI is well described in overhead athletes (eg, baseball players, tennis players, swimmers) but not in gymnasts. We conducted this study to estimate the incidence of any type of shoulder pathology in elite gymnasts, to estimate MDI incidence in this population, and to determine which if any circumstances place these gymnasts at higher risk for developing MDI. An 18-question multiple-choice questionnaire was administered to 70 female US collegiate gymnastics teams. Potential risk factors were cross-matched against those gymnasts with traumatic shoulder injuries and again against those gymnasts who met MDI study inclusion criteria. Of the 1115 questionnaires distributed, 457 (34 teams) were returned. Twenty-two percent of gymnasts suffered from a traumatic shoulder injury, and 11% met study inclusion criteria. There was a statistically significant (P =.02) relationship between generalized ligamentous laxity and traumatic shoulder instability but not MDI. Incidence of atraumatic or traumatic shoulder injuries in gymnasts is higher than previously recognized. Although this study did not reveal any potential risk factors, it does provide several avenues for more specific research.

The inverted nipple: to cut the ducts or not?

Much dilemma exists as whether to divide the lactiferous ducts or not when correcting an inverted nipple. We report a series of 26 cases (44 nipples), which have undergone correction with or without duct division. Eversion was maintained in 59% of nipples. Analysis of the failure groups revealed similar rates of failure for umbilicated nipples whether the ducts were divided (27%) or not (25%). Invaginated nipples showed an increased tendency to reinvert postoperatively if the ducts were not divided (80%) than if they were (42%) (not significant). Permanent loss of nipple sensation was noted in 20% of cases when the lactiferous ducts were divided. Postoperatively two women were able to breast feed despite complete division of their lactiferous ducts. Women with umbilicated nipples are usually able to breast feed. We believe that correction of the umbilicated nipple can usually be successfully performed, and function maintained without dividing the ducts. Correction of the invaginated nipple requires duct division. The underlying pathogenesis and varying methods of correction are reviewed.

Chromic acid burns; beware, be aggressive, be watchful.

Two cases involving the development of systemic toxicity and prolonged wound healing in small percentage area burns to chromic acid are reported. The treatment of chromic acid burns is reviewed and a protocol of management suggested.

Fasciocutaneous island flaps for orthopaedic management in lower limb reconstruction using dermatomal precincts.

This paper describes a technique of fasciocutaneous island flaps used in reconstruction of the lower limb. It is very versatile and some 26 individual flaps in 22 patients have been used to reconstruct skeletal and soft tissue problems from the popliteal fossa to the ankle joint. These longitudinally designed flaps made up of a trilaminate of skin, subcutaneous fat and fascia are aligned within the dermatomal precincts. The most important location for such flap design is along the peroneal compartment sitting within the L5 dermatome and incorporating the superficial peroneal nerve. It can be lengthened as far as the lateral malleolus and is an excellent reconstructive method to close defects over the lower third of the tibia. The medial compartment of the leg employing the saphenous nerve (L4 dermatome) is another area for fasciocutaneous island flap reconstruction, but use is restricted to the upper two-thirds of the tibial area. Posteriorly the island flap design sits along the S2 dermatome, this time incorporating the sural nerve to reconstruct defects of the calf and can be extended to include problems of the popliteal fossa. In the overall flap technique, the age of the patient is not a contraindication and cases with peripheral vascular disease have been treated successfully. The flaps may extend up to a 5:1 ratio in dimension. The operating time can be considerably shortened.

Experience in the surgical management of the hand in dystrophic epidermolysis bullosa.

Between 1981 and 1990, 45 patients (80 hands) underwent 122 hand operations, involving extensive release of contractures and pseudosyndactyly, with split skin grafting of secondary defects. Other procedures included the use of Kirschner wires, tendon release and arthroplasty. A postoperative programme of long term night splintage was employed. Finger extension was significantly improved for up to 5 years postoperatively, with a mean extension deficit preoperatively of 139 degrees, at 1 year postoperatively 60 degrees (p < 0.0001) and 4 years 84 degrees (p < 0.05). Preoperatively, pseudosyndactyly was present in 64.3% of web spaces, in comparison to 13.3% at 1 year, 37% at 4 years (p < 0.01) and 66.6% at 5 years (N.S.) postoperatively. Adduction contracture of the thumb was significantly improved for 2 years postoperatively. Functional assessment of 18 hands showed significant improvement postoperatively.