Total hip replacements (THR) with modular femoral components (stem-neck interface) make it possible to adapt to extramedullary femoral parameters (anteversion, offset, and length) theoretically improving muscle function and stability. Nevertheless, adding a new interface has its disadvantages: reduced mechanical resistance, fretting corrosion and material fatigue fracture. We report the case of a femoral stem fracture of the female part of the component where the modular morse taper of the neck is inserted. An extended trochanteric osteotomy was necessary during revision surgery because the femoral stump could not be grasped for extraction, so that a long stem had to be used. In this case, the patient had the usual risk factors for modular neck failure: he was an active overweight male patient with a long varus neck. This report shows that the female part of the stem of a small femoral component may also be at increased failure risk and should be added to the list of risk factors. To our knowledge, this is the first reported case of this type of failure.

The number of cleft surgeries was found to increase per year, and unilateral cleft lip was identified as the commonest type of cleft cases. Financial, logistic, and training support to cleft clinics in developing countries would play an essential role in the treatment of cleft patients.

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Background: Despite significant advances in cleft lip and palate (CLP) care, the often quoted "rule of 10 s" has not been objectively investigated concerning its practicality since its inception, especially, in low-resourced country like Ghana. Aim of the Study: This was to evaluate the unilateral cleft lip weight, haemoglobin and surgical repair outcome by considering the "Rule of 10's". Materials and Methods: A retrospective study of all consecutive patients who presented with unilateral cleft lip and were operated on during the period 2011 to 2015. The information retrieved from the patient's records included the following at the time of surgery: Age (weeks), weight (pounds), hemoglobin level (g/dl), type of cleft and surgical outcome. Results: A total of 120 patients were seen during the study period (2011 to 2015) that had unilateral cleft lip. Female to male ratio was 3:2. (74) 62% had in addition, cleft palate (UCLp) and (46) 38% were only unilateral cleft lip without a palate (UCLo). Unilateral cleft lip was also divided into complete(UCLc) and incomplete unilateral cleft lip(UCLi). Out of the total number 120 patients seen during the study period, (80) 67% had complete unilateral cleft lip while (40) 33% had incomplete unilateral cleft lip. At week 10, the average weight were 11.2, 8.5, 8.2, 11.8 pounds for the various types of cleft at the time of surgery of the lip (UCLo, UCLp, UCLc and UCLi respectively). ≥10 weeks, the level of Haemoglobin at the time of surgery were 10.5, 8.6, 8.6 and 10.8 gm/dl (UCLo, UCLp, UCLc and UCLi respectively. Most of the patients, 28.4% with an associated cleft palate had their unilateral cleft repairs done by week 15. Conclusion: Children with unilateral cleft lip with an associated palate and unilateral complete cleft lip turned to have lower haemoglobin and weight at week ten after birth compared to unilateral incomplete cleft lip without cleft palate patients. This means that, the rule of 10s is still applicable in our centre especially for those with incomplete unilateral cleft lip without an associated cleft palate. There were more post-operative wound infections in children who had unilateral cleft lip with an associated cleft palate.

Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts. We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P case-parent African trios to identify pathogenic variants that contribute to the risk of clefting. We replicated this analysis using whole-exome sequence data from a Brazilian nsCL ± P cohort. Computational analyses were then used to predict the mechanism by which these variants could result in increased risks for nsCL ± P. We discovered damaging mutations within the AFDN gene, a cell adhesion molecule (CAMs) that was previously shown to contribute to cleft palate in mice. These mutations include p.Met1164Ile, p.Thr453Asn, p.Pro1638Ala, p.Arg669Gln, p.Ala1717Val, and p.Arg1596His. We also discovered a novel splicing p.Leu1588Leu mutation in this protein. Computational analysis suggests that these amino acid changes affect the interactions with other cleft-associated genes including nectins (PVRL1, PVRL2, PVRL3, and PVRL4) CDH1, CTNNA1, and CTNND1. This is the first report on the contribution of AFDN to the risk for nsCL ± P in humans. AFDN encodes AFADIN, an important CAM that forms calcium-independent complexes with nectins 1 and 4 (encoded by the genes PVRL1 and PVRL4). This discovery shows the power of NGS analysis of multiethnic cleft samples in combination with a computational approach in the understanding of the pathogenesis of nsCL ± P.