Current Reviews in Musculoskeletal Medicine: Current Controversies for Treatment of Meniscus Root Tears

Purpose of ReviewThe role of the meniscus in preserving the biomechanical function of the knee joint has been clearly defined. The hypothesis that meniscus root integrity is a prerequisite for meniscus function is supported by the development of progressive knee osteoarthritis (OA) following meniscus root tears (MRTs) treated either non-operatively or with meniscectomy. Consequently, there has been a resurgence of interest in the diagnosis and treatment of MRTs. This review examines the contemporary literature surrounding the natural history, clinical presentation, evaluation, preferred surgical repair technique and outcomes.Recent FindingsSurgeons must have a high index of suspicion in order to diagnose a MRT because of the nonspecific clinical presentation and difficult visualization on imaging. Compared with medial MRTs that commonly occur in middle age/older patients, lateral meniscus root injuries tend to occur in younger males with lower BMIs, less cartilage degeneration, and with concomitant ligament injury. Subchondral insufficiency fractures of the knee have been found to be associated with both MRTs and following arthroscopic procedures. Meniscus root repair has demonstrated good outcomes, and acute injuries with intact cartilage should be repaired. Cartilage degeneration, BMI, and malalignment are important considerations when choosing surgical candidates. Meniscus centralization has emerged as a viable adjunct strategy aimed at correcting meniscus extrusion.SummaryMeniscus root repair results in a decreased rate of OA and arthroplasty and is economically advantageous when compared with nonoperative treatment and partial meniscectomy. The transtibial pull-through technique with the addition of centralization for the medial meniscus is associated with encouraging early results.     

A first-in-human Phase I dose-escalation trial of the novel therapeutic peptide,ALM201, demonstrates a favourable safety profile in unselected patients with ovarian cancer and other advanced solid tumours

Background We aimed to assess the safety, tolerability and pharmacokinetics of a novel anti-angiogenic peptide.Methods We used an open-label, multicentre, dose-escalation Phase I trial design in patients with solid tumours. ALM201 was administered subcutaneously once daily for 5 days every week in unselected patients with solid tumours.Results Twenty (8 male, 12 female) patients with various solid tumours were treated (18 evaluable for toxicity) over eight planned dose levels (10–300 mg). ALM201 was well-tolerated at all dose levels without CTCAE grade 4 toxicities. Adverse events were predominantly grades 1–2, most commonly, localised injection-site reactions (44.4%), vomiting (11%), fatigue (16.7%), arthralgia (5.6%) and headache (11%). Thrombosis occurred in two patients at the 100 mg and 10 mg dose levels. The MTD was not reached, and a recommended Phase II dose (RP2D) based on feasibility was declared. Plasma exposure increased with dose (less than dose-proportional at the two highest dose levels). No peptide accumulation was evident. The median treatment duration was 11.1 (range 3–18) weeks. Four of 18 evaluable patients (22%) had stable disease.Conclusions Doses up to 300 mg of ALM201 subcutaneously are feasible and well-tolerated. Further investigation of this agent in selected tumour types/settings would benefit from patient-selection biomarkers.Subject terms: Drug development, Drug safety     

Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2

A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.     

Screening for depression in pregnant women with HIV infection

OBJECTIVE: To determine the utility of screening for depression in pregnant women with human immunodeficiency virus (HIV) infection. STUDY DESIGN: Women with HIV infection who received prenatal care at an inner-city institution between March 2004 and March 2006 were offered the Beck Depression Inventory (BDI), a screening tool to detect depressive symptomatology. Scores >9 were considered positive. RESULTS: Of 51 subjects who participated, 53% had positive screening scores for depression. Of those whose scores were positive, 33% had no prior history of psychiatric illness. Those in whom HIV was diagnosed during pregnancy had higher mean and median BDI scores than those with HIV diagnosed before pregnancy (21.2 vs. 13.3 and 21 vs. 9.5, respectively; p = 0.049). Two factors were associated with positive screenings: history of psychiatric disease (p = 0.001) and history of substance abuse (p = 0.042). Patients with positive screenings first presented for prenatal care at a later gestational age and had fewer prenatal visits than those without evidence of depression (14.9 vs. 12.0, p = 0.035 and 9.2 vs. 11.3, p = 0.045). More than half (56%) who screened positive received psychological care during the prenatal period. CONCLUSION: Women with HIV infection should routinely be screened for depression during pregnancy. Those with positive screens should be offered formal psychological evaluation.