Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.

BACKGROUND AND OBJECTIVES: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures. METHODS: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis. RESULTS: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases. CONCLUSION: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Craniofacial trauma.

The treatment of combined major dislocations of the face and skull requires a craniofacial team consisting of a plastic maxillofacial surgeon, a neurosurgeon, an anesthesiologist, and radiologists. The best results can only be achieved at the primary intervention both from a functional and an esthetic standpoint. Careful preoperative clinical and radiologic examinations are mandatory to reach these high goals. In primary repair, the cranial approach aims at constructing "a monobloc bone flap" to suture meningeal tears and to reinforce them with a pericranial graft, to close the cranial base completely using cancellous bone grafts, and to exclude the frontal sinuses. The facial skeleton is repaired by constructing a rigid external facial frame and thereafter progressing centrally finishing with the "internal" orbitonasal dislocations. The reconstruction aims at a self-stabilizing bone puzzle fixed with interosseous wires, making external fixation unnecessary. Secondary repair requires osteotomies at fracture sites to reposition malunited fractures and the use of autogenous bone grafts for stabilization.

The step technique for the reconstruction of lower lip defects after cancer resection. A follow-up study of 165 cases.

One hundred and sixty-five patients with localized cancer of the lower lip were excised and reconstructed over a 25-year period using Bengt Johanson's step technique. Eight-eight percent of the tumors were less than 2 cm in size and 65% were of high histopathological differentiation. Fifty-six percent were reconstructed with bilateral step flaps. Nine local recurrences appeared in 5 patients, none of whom died of lip cancer. Eight patients later developed regional metastases and 3 of these patients died of lip cancer. The 5-year survival rate was 98%. The step technique is recommended for reconstruction of lip defects of up to 2/3 of the lower lip and may, in larger resections, be combined with either a fan flap or an Estlander flap. The outstanding functional results are due to the use of adjacent tissue for the reconstruction which preserves the normal arrangement of muscles, vessels and nerves.

Hand function after replantation or revascularization of upper extremity injuries. A follow-up study of 21 cases operated on 1979-1985 in Göteborg.

Twenty-one patients with revascularized/replanted amputated parts of the upper limb were studied for an evaluation of hand function. Two patients had been injured at the lower arm to wrist level, four between the wrist and MCP joint, three distal to the MCP joints in thumbs and/or fingers, and twelve in the thumb only. Hand function was measured as grip and pinch strength, range of movement (ROM), sensibility (two point discrimination), and Sollerman test score. Cold sensitivity as related to circulatory changes in the replanted limb was evaluated in six patients using the critical opening test (COP). Twelve of 17 initiated replantations (71%), and 11 of 12 revascularizations (92%), were successful. Hand function was restricted in patients with amputations at the lower arm to wrist level, fair in replanted midhands, good, but with wide variations after replantations at the MCP or distal II-V fingers, and best of all in replanted thumbs. Sensibility was poor in a majority of the patients. Three out of six of the patients who were COP-tested had significantly reduced blood pressure in the replanted part. The test results (grip, ROM, Sollerman score) in three patients with amputated thumbs were not found to differ greatly from those with replanted thumbs. These results raise the question of whether the Sollerman test underestimates the importance of the thumb or whether the thumb is overestimated in hand function.

Anterior levator resection in congenital genuine blepharoptosis. A follow-up of 55 operated eyelids.

Fifty-five eyelids operated on for congenital blepharoptosis over a 10-year period were followed up, with a mean observation time of seven years. Ptosis was on the right side in 12 patients, the left side in 20, and bilateral in 12. Ptosis was regarded as being slight in 32 eyelids, moderate in 10 and severe in 14. The operative procedure was resection of the levator muscle and its aponeurosis through an anterior approach. Fifty-five percent of the patients with slight ptosis were improved, with the eyelid having a normal position. All the patients with moderate ptosis were improved--half to a normal eyelid position, and half with a residual slight ptosis. All but one patient with severe ptosis were improved, and half of these to a normal eyelid position. It is concluded that this operation can be used for all types of congenital ptosis, and especially in severe cases, where it produces better results than e.g. the frontalis sling procedure.

Simple adaptation of Müller's muscle to the tarsal plate in congenital blepharoptosis. A preliminary report.

Five patients with congenital blepharoptosis have undergone a simple adaptation of Müller's muscle to the tarsal plate. In two patients this led to a good postoperative result, in one to an over-correction, while two were not corrected enough. These results should stimulate further studies on the importance of Müller's muscle in congenital blepharoptosis.

Multiple craniofacial surgical interventions during 25 years of follow-up in a case of giant fibrous dysplasia. Case report.

Fibrous dysplasia may affect the jaws as a monostotic lesion which most often ceases to be active at the end of normal bone growth. In some cases there is no stabilization on completion of normal skeletal growth. This may lead to severe malformation and functional disturbance to the face. In these cases, the patient must be followed regularly and resection of the deformed tissue must be performed repeatedly as the recurrences appear. Attention is also brought to the fact that fibrous dysplasia may be difficult to separate from chronic sclerosing osteomyelitis, a condition that should be treated differently.

The effect of different cooling temperatures and immersion fluids on post-burn oedema and survival of the partially scalded hairy mouse ear.

One ear of NMRI hairy mice was first scalded and then immediately immersed in cold water or saline at 8 degrees C, 15 degrees C, 20 degrees C, 25 degrees C or 30 degrees C for a period of 30 min in order to study oedema formation and the therapeutic effect at 4 days. Oedema was determined by wet-dry weight measurements of punch biopsies from the ear and expressed as an increase in tissue water content. The therapeutic effects at 4 days were determined by observing the survival of the ear; the area of necrosis was expressed in per cent of the total area of the ear. Significant oedema was found in all scalded ears. A partial (15 per cent) dry necrosis of the untreated burned ear had developed within 4 days. Cooling in 8 degrees C water or saline for 30 min post-burn significantly reduced oedema in this model as determined 2h post-burn. However, 4 days post-burn all cooled ears showed a 15 per cent necrosis.

Effects of cooling after scald injury to a dorsal skin fold of mouse.

Shaved trunk skin folds of hairy mice were scalded for 20 s by water immersion. In one set of experiments the effect of increasing burn temperature (51 degrees C-60 degrees C) was studied, in another the folds were first scalded at 51 degrees C-54 degrees C and then immediately cooled for 30 min in 8 degrees C water. Animals were killed 2 h and 4 days postburn. Before sacrifice, Evans blue was injected i.v. to some animals to visualize preserved vascular perfusion and areas of increased permeability. Macroscopic observations (and photographic documentation) were made of the outside and inside of the injured skin and biopsies for light microscopy were obtained centrally in the burns. The injured area was measured by planimetry on photographs and expressed in percent of the whole burned area. At 4 days, brownish, oval areas appeared on the skin being progressively larger with increasing burn temperature. The 51 degrees C burn only resulted in a very small, spotlike, tissue injury, while the greater than or equal to 52 degrees C produced a macroscopic necrosis amounting to 40%-94% of the burned area. Postburn cooling did not reduce the damaged area as recorded 4 days postburn. Histologically, the tissues seemed well preserved at 2 h after 51 degrees C scalds, whereas cell damage was obvious and increasingly pronounced after greater than or equal to 53 degrees C burns. After 52 degrees C burns a mixed picture emerged. A similar microscopic pattern was seen at 4 days; 51 degrees C specimens were undamaged, some 52 degrees C and all greater than or equal to 53 degrees C were necrotic.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinical study of Trypure or Varidase on minor burns.

A prospective double blind study using Varidase or Trypure on 2nd degree local burns in 18 patients was performed. No difference in cleaning or healing effect was revealed. In 6 out of 11 Trypure-treated and 1 out of 12 Varidase-treated patients treatment had to be discontinued because of intolerable pain. This difference was statistically significant.

Latissimus dorsi musculocutaneous flap after excision of radionecrosis in the neck. Case report.

A case is presented where a myocutaneous latissimus dorsi flap was used to cover a defect resulting from irradiation injury to the neck region in a young woman. The advantage of this flap is the donor scar which is less disfiguring than flaps from the anterior chest usually chosen in such cases. The flap is taken the shortest way to the head- and neck region, through the axilla, under the insertion of the major pectoral muscle, and through the trigonum deltoideopectorale.

Postburn blood flow, edema, and survival of the hairy mouse ear after scald injury at different temperatures.

In one group (a) one ear of NMRI hairy mice was scalded in water at 36 degrees C, 39 degrees C, 42 degrees C, 45 degrees C, 48 degrees C, 51 degrees C, 52 degrees C, 53 degrees C, 54 degrees C, 57 degrees C, and 60 degrees C for 20 s, using a new dip burn model, for evaluation of edema formation 2 h postburn. In another group of mice (b) one ear was scalded in the 45 degrees C-60 degrees C interval and the ear studied in a vital microscope repeatedly for 4 days. In a third group (c), one ear was scalded in the 36 degrees C-60 degrees C interval and the microcirculatory flow was recorded by a laser Doppler flowmeter (1Df) for a period of 2 h postburn. In a fourth group of animals (d) one ear was scalded at 53 degrees C or 54 degrees C. In some animals the ear was then cooled in 8 degrees C water or saline for 30 min. Others were treated preburn with cimetidine, Ketanserin, indomethacin or methylprednisolone. Edema was determined in group (a) by wet-dry weight measurements of punch biopsies from both the burned and the contralateral unburned ear and expressed as an increase in tissue water content. The long-term effect was determined by observing the survival of the ears (groups b and d); the area of necrosis was expressed as a percentage of the total area of the ear. Significant edema was formed in ears immersed in 48 degrees C to 60 degrees C water with a maximum after 53 degrees C burns.(ABSTRACT TRUNCATED AT 250 WORDS)

A morphological and histochemical study of the scalded hairy mouse ear.

The right ear of mice was scalded at 51 degrees C and 53 degrees C for 20 s, using the recently developed dip burn model, and examined morphologically and histochemically at intervals for 2 h postburn. The left, unburned ear served as control. Burned ears intended for light and electron microscopy were fixed in situ by means of vascular perfusion. Ears for histochemical studies were cut off and immediately frozen at -140 degrees C. The enzyme histochemical analyses comprised a variety of oxido-reductases and hydrolases. After a 51 degrees C scald, scattered epidermal cell damage was observed with intracellular edema and mitochondrial destruction. Most microvessels were patent. Scalding with 53 degrees C water produced extensive cellular changes in the epidermis from 5 min including mitochondrial alterations, tonofilament aggregation and intercellular separations, progressing into complete epidermal destruction and lysis at 2 h postburn. Morphologically, many microvessels were occluded by cellular aggregates or debris after endothelial cell destruction. Of the histochemical assays the test for succinic dehydrogenase gave conclusive results that correlated well with the morphological findings, indicating partial dysfunction of epidermal cells 2 h postburn after a 51 degrees C scald and early, almost total absence of activity from 5 min postburn after a 53 degrees C scald injury. Scalding at 53 degrees C invariably leads to ear necrosis. This might be explained by the epidermal destruction, which in turn seems related to mitochondrial viability, and microcirculatory blood flow. The sensitivity of this experimental model precludes direct comparisons with studies of scalds to skin covering large tissue volumes.

Effect of cold water immersion on oedema formation in the scalded mouse ear.

One ear of adult white NMRI hairy mice was first scalded and then immersed in cold water in order to study the effect of cooling on oedema formation. Oedema was determined by wet-dry weight measurements of punch biopsies from the ear and expressed as an increase in tissue water content. The temperature of the cold water was 8 degrees C and periods of cooling from 15 to 240 minutes were used. The contralateral ear and the quadriceps muscle were used to study distant effects of scalding and cooling. After scalding, significant oedema was found in the burned ear. Cooling for 30 minutes gave a significant reduction of oedema in this model. Shorter or longer periods of cooling did not reduce oedema significantly. Cooling did not influence the oedema formation of the contralateral (unburned ear). Neither scalding nor cooling changed the water content of the muscle.