Osseointegrated total knee replacement connected to a lower limb prosthesis: 4 cases

Background and purpose — Osseointegrated implants are an alternative for prosthetic attachment in individuals with amputation who are unable to wear a socket. However, the load transmitted through the osseointegrated fixation to the residual tibia and knee joint can be unbearable for those with transtibial amputation and knee arthritis. We report on the feasibility of combining total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment.Patients and methods — We retrospectively reviewed all 4 cases (aged 38–77 years) of transtibial amputations managed with osseointegration and TKR in 2012–2014. The below-the-knee prosthesis was connected to the tibial base plate of a TKR, enabling the tibial residuum and knee joint to act as weight-sharing structures. A 2-stage procedure involved connecting a standard hinged TKR to custom-made implants and creation of a skin-implant interface. Clinical outcomes were assessed at baseline and after 1–3 years of follow-up using standard measures of health-related quality of life, ambulation, and activity level including the questionnaire for transfemoral amputees (Q-TFA) and the 6-minute walk test.Results — There were no major complications, and there was 1 case of superficial infection. All patients showed improved clinical outcomes, with a Q-TFA improvement range of 29–52 and a 6-minute walk test improvement range of 37–84 meters.Interpretation — It is possible to combine TKR with osseointegrated implants.Socket-related discomfort leads to a significant reduction in the quality of life of individuals with lower limb amputation (Dillingham et al. 2001, Gholizadeh et al. 2014). Socket-skin interface problems lead to poor fit, diminished proprioception in the amputated limb, lack of rotational control, and reduction of ipsilateral proximal joint movement (Legro et al. 1999, Lyon et al. 2000, Meulenbelt et al. 2006).A direct connection of the prosthetic limb to the bone using osseointegrated implants can address these socket-related problems (Van de Meent et al. 2013, Tsikandylakis et al. 2014). Brånemark introduced this surgical procedure in 1995. He adapted osseointegration principles established in dental surgery to the rehabilitation of individuals with transfemoral amputation using a percutaneous bone anchoring implant screwed into the femur (Brånemark et al. 2001). Hip replacement spongiosa surface coating technology has been used to make a chrome cobalt intramedullary press-fit implant (Endo-Exo Prosthesis) allowing larger surface area for osseointegration and faster rehabilitation (Staubach and Grundei 2001). Al Muderis et al. (2015) adapted highly porous plasma-sprayed titanium implants to provide optimum initial press-fit and solid bone ingrowth.Studies of transfemoral implants have found improved quality of life, prosthetic use, body image, hip range of motion, sitting comfort, and walking ability (Van de Meent et al. 2013, Hagberg et al. 2014). For example, substantial improvements in health-related quality of life using the Global component of the questionnaire for transfemoral amputees (Q-TFA)—of 38 points (Hagberg et al. 2014) and 24 points (Van de Meent et al. 2013)—have been reported in 2 case series of 51 and 22 patients, respectively.Similar benefits could be expected for transtibial amputees using osseointegrated implants, as the knee joint could possibly enhance their gait. A study of 39 cases involving upper and lower limb prostheses (Tillander et al. 2010) found infections in 7 patients at an average follow-up period of 54 (3–132) months, with no infections reported for 1 tibial implant. At our own center, preliminary evidence of the safety and effectiveness of the tibial impants in 22 transtibial amputees with a minimum of 6 months of follow-up gave results consistent with the published results for transfemoral amputations (Khemka et al. 2015).Few authors have reported on the safety of this procedure (Brånemark et al. 2014, Tsikandylakis et al. 2014). One of the largest studies included 51 patients and reported superficial infections in approximately half of these patients at 2-year follow-up. In that study, the implant was removed in 1 patient due to deep infection and in 3 patients due to aseptic loosening (Brånemark et al. 2014).Osseointegrated implants are not currently recommended for transtibial amputees with ultra-short residuum. In addition to the practical technical challenges, biomechanical studies have suggested that small bone-implant contact is more likely to increase the risk of loosening (Lohr et al. 2000, Henriksen et al. 2003, Carvalho et al. 2012). Osseointegration is also not currently recommended for those suffering from ipsilateral knee osteoarthritis because it is hypothesized that an osseointegrated tibial implant will aggravate arthritic symptoms due to mechanical forces (Frossard et al. 2008).We describe the surgical procedure and early results of combining a total knee replacement (TKR) with an osseointegrated implant for prosthetic attachment for the first time.     

Prevalence of Hypertension in Patients with Type II Diabetes in Referral versus Primary Care Clinics

We compared the prevalence of hypertension in patients with non–insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication.

Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model.

The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.     

病理在肺癌治疗中的关键角色

在过去的十年中,我们对于肺癌生物学和治疗的认识取得了显著进步。识别肺癌发生的关键驱动事件对其靶向治疗的发展作出了贡献,预示着肺癌的个性化医疗时代的到来。因此,病理分型和分子检测变得至关重要,而日益增加的检测需求往往是基于小的诊断标本。这使得国际肺癌研究学会/美国胸科学会/欧洲呼吸学会[The International association for the study of cancer (IASLC)/American thoracic society (ATS)/European respiratory society (ERS)]对小活检/细胞学肺癌标本的第一次结构分类进行了审视和推动,并且提出了肺腺癌的新分类。这些都提高了病理诊断的临床相关性,强调了现代外科病理学家作为多学科团队中成员的作用,在肺癌患者的临床试验和确定适当和及时的治疗中发挥了决定性作用。     

Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population

Benznidazole is the frontline drug used against Trypanosoma cruzi, the causative agent of Chagas disease. However, treatment failures are often reported. Here, we demonstrate that independently acquired mutations in the gene encoding a mitochondrial nitroreductase (TcNTR) can give rise to distinct drug-resistant clones within a single population. Following selection of benznidazole-resistant parasites, all clones examined had lost one of the chromosomes containing the TcNTR gene. Sequence analysis of the remaining TcNTR allele revealed 3 distinct mutant genes in different resistant clones. Expression studies showed that these mutant proteins were unable to activate benznidazole. This correlated with loss of flavin mononucleotide binding. The drug-resistant phenotype could be reversed by transfection with wild-type TcNTR. These results identify TcNTR as a central player in acquired resistance to benznidazole. They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies.     

Periodontal Treatment Combined With Tongue Cleaning Reduces Oral Malodor Among Patients With Periodontitis, Whereas for Patients With Gingivitis, Tongue Cleaning Alone is Sufficient

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Clinical trial of oral malodor treatment in patients with periodontal diseases. Pham TA, Ueno M, Zaitsu T, Takehara S, Shinada K, Lam PH, Kawaguchi Y. J Periodontal Res 2011;46:722-9. REVIEWERS: Khady Ka, DDS, MSc, and Belinda Nicolau, DDS, PhD PURPOSE/QUESTION: To what extent do periodontal treatment and tongue cleaning reduce oral malodor among patients with periodontitis and patients with gingivitis? SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Randomized controlled trial LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable.     

Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells

The BH3-mimetic ABT-737 and an orally bioavailable compound of the same class, navitoclax (ABT-263), have shown promising antitumor efficacy in preclinical and early clinical studies. Although both drugs avidly bind Bcl-2, Bcl-x(L), and Bcl-w in vitro, we find that Bcl-2 is the critical target in vivo, suggesting that patients with tumors overexpressing Bcl-2 will probably benefit. In human non-Hodgkin lymphomas, high expression of Bcl-2 but not Bcl-x(L) predicted sensitivity to ABT-263. Moreover, we show that increasing Bcl-2 sensitized normal and transformed lymphoid cells to ABT-737 by elevating proapoptotic Bim. In striking contrast, increasing Bcl-x(L) or Bcl-w conferred robust resistance to ABT-737, despite also increasing Bim. Cell-based protein redistribution assays unexpectedly revealed that ABT-737 disrupts Bcl-2/Bim complexes more readily than Bcl-x(L)/Bim or Bcl-w/Bim complexes. These results have profound implications for how BH3-mimetics induce apoptosis and how the use of these compounds can be optimized for treating lymphoid malignancies.     

Complex craniosynostosis is associated with the 2p15p16.1 microdeletion syndrome

In a screening project of patients with (complex) craniosynostosis using genomic arrays, we identified two patients with craniosynostosis and microcephaly with a deletion in the 2p15p16.1 chromosomal region. This region has been associated with a new microdeletion syndrome, for which patients have various features in common, including microcephaly and intellectual disability. Deletions were identified using Affymetrix 250K SNP array and further characterized by fluorescence in situ hybridization (FISH) analysis and qPCR. The deletions in our two patients overlapped within the 2p15p16.1 microdeletion syndrome area and were 6.8 and 6.9 Mb in size, respectively. FISH and qPCR confirmed the presence of only one copy in this region. Finemapping of the breakpoints indicated precise borders in our patients and were further finemapped in two other previously reported patients. Clinical features of patients with deletions in the 2p15p16.1 region vary. Including data from our patients, now eight out of nine reported patients have microcephaly, one of the major features, and all had intellectual disability. The current reported two patients add different forms of craniosynostosis to the clinical spectrum of this recently recognized microdeletion syndrome. © 2013 Wiley Periodicals, Inc.     

Empleo,eficacia y repercusión clínica del apoyo radiológico al diagnóstico de la apendicitis aguda

Objective

The aim of this study is to analyze the increasing need of radiological support in the diagnosis of acute appendicitis (AA), the clinical repercussions associated, and the parameters of diagnostic accuracy of ultrasound and computed tomography (CT) scan for AA.

Material and methods

Observational and analytical study. Cohort, patients operated on for suspected AA at a tertiary referral hospital. Pregnancy and <14 years were exclusion criteria. Study group: January 2010-December 2011 (n1 = 419). Control group: set of patients aged 18 to 65 years old operated between October 2001-September 2003 (n2 = 237). Variables analyzed in both groups: 1) percentage of radiological support for diagnosis of acute appendicitis; 2) sensitivity and positive predictive value (PPV) of ultrasound and CT scan; 3) rate of surgical explorations with negative result or with diagnosis other than acute appendicitis. Statistical analysis: SPSS software, χ² test, statistical significance accepted with P<.05, 95% confidence interval (95% CI) for the odds ratio (OR).

Results

Age, gender, percentage of atypical locations and gangrenous/perforated episodes were similar in both groups. The number of radiological examinations needed for diagnosis was significantly higher in the study group (78.8% vs. 30.4%, P<.0,000). Sensitivity was significantly superior for CT than for ultrasound scan (97% vs. 86%), but PPV was similar in both tests (92% vs. 94%). Surgical exploration percent values with diagnosis of acute appendicitis was significantly higher in the study group (94.5% vs. 88.6%; P<.006, OR 2.2; CI 95% 1.25-4).

Conclusions

CT and ultrasound scan are excellent diagnostic tools for acute appendicitis, and have contributed to a significant increase in surgical explorations with correct diagnosis.