Decreased expression of miR‐204‐3p in peripheral blood and wound margin tissue associated with the onset and poor wound healing of diabetic foot ulcers

To investigate the relationship between small non‐coding RNA‐204‐3p (miR‐204‐3p) and the onset and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, sixty four newly diagnosed patients with T2DM without DFU (T2DM group), 82 T2DM patients with DFU (DFU group), and 60 controls with normal glucose tolerance (NC group) were included. Quantitative real‐time PCR (qRT‐PCR) method was used to determine miR‐204‐3p expression levels in peripheral blood and wound margin tissue of subjects, and to analyse the relationship between the expression of miR‐204‐3p and wound healing. In vitro experiments were also performed to understand the effect of miR‐204‐3p on high glucose induced injury of HaCaT cells (human keratinocytes). The results showed that miR‐204‐3p expression level of peripheral blood in the T2DM group was marked lower than that in the NC group [2.38 (1.31‐5.04) vs 3.27 (1.51‐6.98)] (P < .05). Similarly, the miR‐204‐3p expression level of peripheral blood in the DFU group was significantly lower than the T2DM group [1.15 (0.78‐2.89) vs 2.38 (1.31‐5.04)] (P < .01). The expression level of miR‐204‐3p in peripheral blood and wound margin tissues of DFU patients was positively correlated with the healing rate of foot ulcers after 8 weeks (P < .05). Multifactorial logistic regression analysis showed that decreased expression of miR‐204‐3p in peripheral blood was an independent risk factor for DFU (OR = 2.95, P < .05). The results of in vitro experiments showed that miR‐204‐3p could improve the proliferation and migration of HKC cells and reduce the proportion of apoptosis of HKC cells by targeted regulation of zinc finger protein Kruppel like factor 6 (KLF6) in high glucose environment. Therefore, the decreased expression of miR‐204‐3p in peripheral blood and wound tissue of T2DM patients is closely related to the occurrence and poor wound healing of DFU. The down‐regulated expression of miR‐204‐3p can reduce its ability to antagonise the functional damage of keratinocytes induced by high‐glucose conditions. These results will provide potential targets for the treatment of DFU.     

Spine‐Pelvis‐Hip Alignments in Degenerative Spinal Deformity Patients and Associated Procedure of One‐Stage Long‐Fusion with Multiple‐Level PLIF or Apical‐Vertebra Three Column Osteotomy–a Clinical and Radiographic Analysis Study

ObjectiveTo explore the spine‐pelvis‐hip alignments in degenerative spinal deformity (DSD) patients, and compare the outcomes in the procedure of long‐fusion with posterior lumbar inter‐body fusion (PLIF) or single‐level three‐column osteotomy (STO) at lower lumbar level (LLL, L₃‐S₁) and thoracolumbar levels (TLL, T₁₀‐L₂) for those patients.MethodsThis is a retrospective study. Following institutional ethics approval, a total of 83 patients (Female, 67; Male, 16) with DSD underwent long‐fusion with PLIF or STO surgery between March 2015 and December 2017 were reviewed. All of those patients were assigned into LLL and TLL groups. The average age at surgery was 65.2 years (SD, 8.1). Demographic (age, gender, BMI, and comorbidities), radiographs (both coronal and sagittal parameters) and health‐related quality of life (HRQOL) assessments were documented. The radiographic parameters and HRQOL‐related measurements at pre‐ and post‐operation were compared with paired‐samples t test, and those variables in the two groups were analyzed using an independent‐sample t test. The relationships between pelvic incidence (PI) and other sagittal parameters were investigated with Pearson correlation analysis. The Pearson χ² or Fisher''s exact was carried out for comparison of gender, incidence of comorbidities and post‐operative complications.ResultsThere were 53 and 30 patients in the LLL and TLL groups respectively. Those spino‐pelvic radiographic parameters had significant improvements after surgeries (P < 0.001). The patients in the two group with different pre‐operative thoracolumbar kyphosis (TLK, P = 0.003), PI (P = 0.02), and mismatch of PI minus lumbar lordosis (PI‐LL, P = 0.01) had comparable post‐operative radiographic parameters except PI (P = 0.04) and pelvic‐femur angle (PFA, P = 0.02). Comparing the changes of those spine‐pelvic‐hip data during surgeries, the corrections of TLK in TLL group were significant larger (P = 0.004). Pearson correlation analysis showed that there were negative relationship between PI and TLK (r = −0.302, P = 0.005), positive relationship between PI and LL (r = 0.261, P = 0.016) at pre‐operation. Those patients underwent the surgical procedure that long‐segment instrumentation and fusion with STO would have higher incidence of complications involving longer operative timing (P = 0.018), more blood loss (P < 0.001), revision surgery (P = 0.008), and cerebrospinal fluid leakage (P = 0.001). All the HRQOL scores significantly improved at final follow‐up (P < 0.001), with no difference of intra‐group.ConclusionPatients suffered de‐novo scoliosis or hyper‐kyphosis with low PI would be vulnerable to significant thoracolumbar degeneration, and have more changes of spine‐pelvis‐hip data after long‐fusion surgery, however, those with high PI would be closed to significant lumbar degeneration. Although spine‐pelvis‐hip alignments in DSD patients can be restored effectively after long‐fusion with PLIF or STO, the incidence of complications in patients underwent STO was significant higher than that in patients performed multi‐level PLIF.     

24‐Month HIV‐free survival among HIV‐exposed Infants in Lesotho: the PEAWIL cohort study

IntroductionFollowing the implementation of the provision of lifelong antiretroviral therapy to all HIV‐positive pregnant or breastfeeding women for prevention of mother‐to‐child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we assessed the effectiveness of this approach by evaluating 24‐month HIV‐free survival among HIV‐exposed infants (HEIs).MethodsWe conducted a prospective observational cohort study that enrolled HIV‐positive and HIV‐negative pregnant women, with follow‐up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014 and follow‐up ended in September 2018. Trained nurses collected study information through patient interviews and chart abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission and HIV‐free survival rates were computed using Kaplan–Meier estimation. Cox regression hazard models were used to identify factors associated with infant HIV infection and death.ResultsBetween June 2014 and February 2016, we enrolled 653 HIV‐positive and 941 HIV‐negative pregnant women. Twenty‐seven HIV‐negative women acquired HIV during follow‐up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%) female, 3 missing) and 839 who remained HIV‐unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were followed; 550 HEIs and 701 HUIs completed the 24‐month follow‐up period. Of 607 (95.7%) HEIs who were tested for HIV at least once during follow‐up, 17 were found to be HIV‐positive. Two (9.5%) of 21 infants born to mothers who acquired HIV infection during follow‐up were HIV‐positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection. The risk of HIV transmission from HIV‐positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7). The estimated 24‐month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3) among HUIs (Log‐rank p = 0.065). HIV‐free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and birth weight were independently associated with increased HIV infection or death of infants.ConclusionsThe implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV transmission, but survival of HEI remains lower than their HIV uninfected counterparts.     

Role of D‐dimer and Fibrinogen in the Diagnosis of Periprosthetic Joint Infection: A Systematic Review and Meta‐Analysis

The diagnostic potential of D‐dimer and fibrinogen to detect periprosthetic joint infection (PJI) of the hip and knee is not well‐understood. The aim of this study was to determine whether D‐Dimer and fibrinogen can be used as effective biomarkers to screen PJI. A systematic review of the literature indexed in Web of Science, PubMed, Cochrane Library, Embase, and Google Scholar databases was performed. All studies using D‐dimer levels in serum or plasma, or fibrinogen levels in plasma, for the diagnosis of PJI were included. Meta‐analysis estimates, including sensitivity, specificity, diagnostic odds ratios (DOR), and the area under the summary receiver operating characteristic curve (AUSROC), were calculated using a random‐effects model, and used to assess the diagnostic accuracy of these biomarkers. A total of nine studies were analyzed, and their quality was considered to be acceptable. D‐dimer gave a limited diagnostic value if serum and plasma combined: sensitivity (0.77, 95% confidence interval [CI] [0.63 to 0.87]), specificity (0.67, 95% CI [0.54 to 0.78]), DOR (6.81, 95% CI [2.67 to 17.37]), and AUSROC (0.78, 95% CI [0.74 to 0.82]). Plasma D‐dimer levels were associated with less satisfactory sensitivity (0.65, 95% CI 0.57 to 0.71), specificity (0.58, 95% CI 0.50 to 0.66), DOR (2.52, 95% CI 1.64 to 3.90), and AUSROC (0.65, 95% CI 0.61 to 0.69). Serum D‐dimer levels showed higher corresponding values of 0.89 (95% CI 0.79 to 0.94), 0.76 (95% CI 0.55 to 0.89), 24.24 (95% CI 10.07 to 58.32), and 0.91 (95% CI 0.88 to 0.93). Plasma fibrinogen showed acceptable corresponding values of 0.79 (95% CI 0.70 to 0.85), 0.73 (95% CI 0.57 to 0.85), 10.14 (95% CI 6.16 to 16.70), and 0.83 (95% CI 0.79 to 0.86). Serum D‐dimer may be an effective marker for the diagnosis of PJI in hip and knee arthroplasty patients, and it may show higher diagnostic potential than plasma fibrinogen. Plasma D‐dimer may have limited diagnostic potential.     

Reduction with Pre‐Drilling Combined with a Finger Reduction Tool in Difficult‐to‐Reduce Intertrochanteric Fracture

ObjectiveTo investigate the feasibility of pre‐drilling combined with a finger reduction tool for the reduction of difficult‐to‐reduce intertrochanteric fractures.MethodsPatients diagnosed with complicated intertrochanteric fractures during the period from July 2016 to May 2021 at the Affiliated Hospital of our College were enrolled in this study. All patients underwent reduction by pre‐drilling combined with a finger reduction tool followed by fixing with proximal femoral nail antirotation. The outcome of reduction was evaluated by intraoperative fluoroscopy. The operation time, intraoperative fluoroscopy frequency, and incidence of postoperative complications (including infection in the incision area, coxa vara, nail withdrawal, nail breakage, blade cut‐out, lower limb vein thrombosis, and pulmonary embolism) were recorded to evaluate the speed of the operation, the difficulty of the operation, and the prognosis of the patient, respectively. The Harris hip score at 9 months after surgery was used to evaluate the hip recovery.ResultsA total of 52 patients (17 men and 35 women), 61–88 (77.54 ± 7.40) years of age were included in the study. There were 14 patients with cardiovascular or cerebrovascular disease, ten patients with diabetes, three patients with Parkinson''s disease, and three patients with respiratory diseases. The fractures included in the study were classified according to the Orthopedic Trauma Association 31 classification system as type A2.2 (n = 36) or type A2.3 (n = 16). The time from injury to surgery was 1–11 (3.35 ± 1.78) days, and the operation time ranged 31–101 (65.67 ± 14.17) min. The intraoperative blood loss ranged from 40 to 100 (67.69 ± 18.24) mL, and the number of intraoperative fluoroscopy images obtained was 12 to 32 (20.42 ± 5.27). The Harris hip score at 9 months after surgery ranged from 84 to 94 (90.06 ± 2.15). Patients were followed for 9–16 (10.63 ± 1.61) months. One patient died of acute myocardial infarction at 9 months after surgery. One patient suffered from nail withdrawal 5 months post‐operation and thus underwent hemiarthroplasty.ConclusionsSatisfactory reduction can be achieved using a pre‐drilling femoral trochanter combined with a finger reduction tool for the management of difficult‐to‐reduce complex intertrochanteric fractures. This technique does not increase surgical trauma and also reduces the dose of radiation administered to the patient.     

Negative‐pressure wound therapy for donor‐site closure in radial forearm free flap: A systematic review and meta‐analysis

Negative‐pressure wound therapy (NPWT) is often used for skin graft site dressing, and several studies have reported that its use improves skin graft failure in the forearm flap donor site. The present systematic review aimed to evaluate the efficacy of NPWT with skin graft for donor‐site closure in radial forearm free flap (RFFF) reconstruction. A systematic search in PubMed, Web of Science, and Cochrane Library databases was conducted. The search terms used for PubMed were ([radial forearm]) AND ([donor]) AND ([negative pressure or vacuum]). This review was registered in the International Prospective Register of Systematic Reviews and performed in accordance with the preferred reporting items for systematic reviews and meta‐analyses statement. Three prospective randomised controlled trials and three retrospective comparative studies were included. Compared with conventional bolster dressing, the use of NPWT dressing did not lead to significant improvements in partial skin graft loss, tendon exposure, and other complications. NPWT improved hand functionality earlier; nonetheless, the cost of the device and dressings was a disadvantage. The use of NPWT for skin graft fixation in the RFFF donor site is not generally recommended.     

Timing of HIV testing among pregnant and breastfeeding women and risk of mother‐to‐child HIV transmission in Malawi: a sampling‐based cohort study

IntroductionPregnant women living with HIV can achieve viral suppression and prevent HIV mother‐to‐child transmission (MTCT) with timely HIV testing and early ART initiation and maintenance. Although it is recommended that pregnant women undergo HIV testing early in antenatal care in Malawi, many women test positive during breastfeeding because they did not have their HIV status ascertained during pregnancy, or they tested negative during pregnancy but seroconverted postpartum. We sought to estimate the association between the timing of last positive HIV test (during pregnancy vs. breastfeeding) and outcomes of maternal viral suppression and MTCT in Malawi’s PMTCT programme.MethodsWe conducted a two‐stage cohort study among mother–infant pairs in 30 randomly selected high‐volume health facilities across five nationally representative districts of Malawi between 1 July 2016 and 30 June 2017. Log‐binomial regression was used to estimate prevalence ratios (PR) and risk ratios (RR) for associations between timing of last positive HIV test (i.e. breastfeeding vs. pregnancy) and maternal viral suppression and MTCT, controlling for confounding using inverse probability weighting.ResultsOf 822 mother–infant pairs who had available information on the timing of the last positive HIV test, 102 mothers (12.4%) had their last positive test during breastfeeding. Women who lived one to two hours (PR = 2.15; 95% CI: 1.29 to 3.58) or >2 hours (PR = 2.36; 95% CI: 1.37 to 4.10) travel time to the nearest health facility were more likely to have had their last positive HIV test during breastfeeding compared to women living <1 hour travel time to the nearest health facility. The risk of unsuppressed VL did not differ between women who had their last positive HIV test during breastfeeding versus pregnancy (adjusted RR [aRR] = 0.87; 95% CI: 0.48 to 1.57). MTCT risk was higher among women who had their last positive HIV test during breastfeeding compared to women who had it during pregnancy (aRR = 6.57; 95% CI: 3.37 to 12.81).ConclusionsMTCT in Malawi occurred disproportionately among women with a last positive HIV test during breastfeeding. Testing delayed until the postpartum period may lead to higher MTCT. To optimize maternal and child health outcomes, PMTCT programmes should focus on early ART initiation and providing targeted testing, prevention, treatment and support to breastfeeding women.     

Fourth‐Generation Ceramic‐on‐Ceramic THA in Patients with Ankylosing Spondylitis: A Minimum 10‐Year Follow‐Up

ObjectiveTo report the long‐term outcomes of total hip arthroplasty (THA) with fourth‐generation ceramic‐on‐ceramic (CoC) bearing in patients with ankylosing spondylitis (AS).MethodsWe retrospectively identified 180 primary THAs performed in 110 patients with AS, including 100 (90.9%) men and 10 women (9.1%), from 2009 to 2011.The mean age of the patients at surgery was 33 years (range, 16 to 65 years). Cementless prostheses with fourth‐generation CoC bearings were used in all patients. Survivorship of the implants and postoperative complications were calculated. Functional improvement was assessed by the hip flexion‐extension range of motion (ROM) and Harris hip score (HHS). A special noise assessment questionnaire was performed at the last follow‐up. The cumulative incidence of noise was calculated by the Kaplan–Meier method with 95% confidence intervals (CIs). Clinical characteristics and functional outcomes were compared in the hips with noise to those without noise.ResultsThe mean follow‐up was 11 years (range, 10 to 12 years), and survivorship of the implants was 99.4% at the most recent follow‐up. The complications included dislocation (one hip, 0.6%), periprosthetic joint infection (one hip, 0.6%), mild to moderate pain (five hips, 2.8%), heterotopic ossification (12 hips, 6.7%), and noise (52 hips, 28.9%). The flexion‐extension ROM improved significantly with a median from 10° (range, 0 ~ 130°) to 100° (30 ~ 130°) after THA (p < 0.001), and the HHS increased significantly from 41 ± 20 to 90 ± 8 (p < 0.001). The cumulative incidence of noise at 0.5, 5, and 10 years was 6.1% (95% CI, 2.6 ~ 9.6), 16.7% (95% CI, 11.2 ~ 22.1), and 28.9% (95% CI, 22.2 ~ 35.5), respectively, and that of squeaking at 0.5, 5, and 10 years was 4.4% (95% CI, 1.4 ~ 7.4), 13.3% (95% CI, 8.4 ~ 18.3), and 23.9% (95% CI, 17.6 ~ 30.1), respectively. None of the patients with noise generation in the hip reported it affecting daily activities or causing dissatisfaction. No differences in age, sex, BMI, disease duration, bilateral THA, the frequency of bony ankylosis, the proportion of using a 36‐mm‐diameter femoral head, pre/postoperative flexion‐extension ROM, or pre/postoperative HHS were found between hips with noise and those without noise (p > 0.05).ConclusionTHAs with fourth‐generation CoC bearings exhibit excellent long‐term survival and clinical outcomes in patients with AS, with a very low dislocation rate. The incidence of noise associated with CoC bearings in THA performed in patients increases over time, but it does not affect postoperative hip function or daily activities.     

Mid‐ and Long‐Term Follow‐Up Efficacy Analysis of 3D‐Printed Interbody Fusion Cages for Anterior Cervical Discectomy and Fusion

ObjectiveTo evaluate the safety and stability of 3D‐printed interbody fusion cages (3D‐printed cages) in anterior cervical discectomy and fusion (ACDF) by investigating the mid‐ and long‐term follow‐up outcomes.MethodsIn this prospective study, the clinical data of 30 patients with CSM admitted to the Second Hospital of Shanxi Medical University from May 2012 to May 2014 were analyzed. The cohort comprised 18 males and 12 females with an average age of 60.22 ± 3.2 years. All patients were examined by X‐ray, CT and MRI before the operation. A total of 30 cases of CSM were treated by ACDF with 3D printed cage implantation. Mid‐ and long‐term follow‐ups were performed after the surgery. Clinical efficacy was evaluated by comparing the JOA score, SF‐36 score, change in neurological function, cervical curvature index (CCI), vertebral intervertebral height (VIH) and fusion rate before the operation, 6 months after the operation, and at the last follow‐up.ResultsTwo of the 30 patients were lost to follow‐up. The remaining patients were followed up for 48–76 (65.23 ± 3.54) months. The patients recovered satisfactorily with a significant clinical effect. The JOA score increased meanfully and the improvement rate was 89.4% at the final follow‐up. The SF‐36 score increased significantly from pre‐ to postoperatively. The height of the intervertebral space at the last follow‐up was not statistically significantly different from that at 6 months after surgery (P > 0.05), showing that the height of the intervertebral space did not change much and the severity of cage subsidence (CS) decreased. The CCI improved from pre‐ to postoperatively. The CCI did not change much from the 6‐month follow‐up to the last follow‐up. and the cage rate (CR) was 100% at the 6‐month and last follow‐ups. No severe complications, such as spinal cord injury, esophageal fistula, cerebrospinal fluid leakage, cervical hematoma or wound infection, occurred in any of the patients.ConclusionThe clinical and radiological results show that the application of 3D‐printed cages in ACDF can significantly relieve symptoms. Moreover, 3D‐printed cages can restore the curvature of the cervical spine, effectively maintain the intervertebral height for a long time, and prevent complications related to postoperative subsidence.     

Effect of Resistance Training Combined with Beta‐Hydroxy‐Beta‐Methylbutyric Acid Supplements in Elderly Patients with Sarcopenia after Hip Replacement

ObjectivesTo evaluate the efficacy of resistance training (RT) combined with beta‐hydroxy‐beta‐methylbutyric acid (HMB) in the treatment of elderly patients with sarcopenia after hip replacement.MethodsFrom January 1, 2018 to December 31, 2018, 200 elderly patients (68 men, mean age 76.3 years and 137 women, mean age 79.1 years) who experienced femoral neck fracture with sarcopenia after hip arthroplasty were assigned to four groups: RT + HMB group, RT group, HMB group, and negative control group. Baseline data, body composition, grip strength, Barthel index (BI), Harris hip score (HHS), and visual analog scale score (VAS) were compared among the four groups before and 3 months after surgery.ResultsA total of 177 participants completed the trial, including 43 in the HMB + RT group, 44 in the HMB group, 45 in the RT group, and 45 in the negative control group. At the 3‐month follow‐up, the body composition and grip strength of the HMB + RT group and RT group were significantly improved compared with those before operation. The HMB group had no significant change, while the measures in the negative control group significantly decreased. Postoperative BI and HSS did not reach pre‐injury levels in any of the four groups, but postoperative VAS score was significantly improved. However, there was no significant difference in BI, HSS, or VAS among the four groups.ConclusionRT, with or without HMB supplementation, can effectively improve body composition and grip strength in elderly patients with sarcopenia after hip replacement at short‐term follow‐up. Simultaneously, use of exclusive HMB supplementation alone may also help to prevent decreases in muscle mass and grip strength in these patients.     

Three‐Dimensional Distribution of Bone‐Resorption Lesions in Osteonecrosis of the Femoral Head Based on the Three‐Pillar Classification

ObjectiveTo investigate three‐dimensional distribution of bone‐resorptive lesions based on the three‐pillar classification and its effect on the disease progression of osteonecrosis of the femoral head (ONFH).MethodsA total of 194 femoral head CT images from 117 patients diagnosed with ARCO stage II and III ONFH were retrospectively reviewed from April 2014 to February 2019. Three‐dimensional structures of the femoral head and the bone‐resorptive lesions were reconstructed. Using the three‐pillar classification and coronal plane of the femoral head, we divided each femoral head into six regions to observe the location characteristics of bone‐resorption lesions, and explore the destruction of different areas of the femoral head by the bone‐resorptive lesions. Then the hips were divided into two groups based on whether they contained bone‐resorption lesions and compared the difference of stage II and stage III between the two groups.ResultsThe regional distribution revealed 39 (27.27%), 55 (38.46%), six (4.20%), 23 (16.08%), 17 (11.89%) and three (2.10%) bone‐resorptive lesions in regions I, II, III, IV, V and VI respectively. The lateral pillar, AL (I + IV), contained 44.76% of the lesions, central pillar, C (II + V), 48.95%, and medial pillar, M (III + VI), 6.29%. Moreover, there were 81.82% bone‐resorption lesions in anterolateral pillar, AL (I + II + IV), and 18.18% in posteromedial pillar, PM (III + V + VI). In all ONFH hips, the lateral pillar of 81(88.04%) femoral heads were affected, the central pillar of 84 (91.30%) femoral heads were affected, and the medical pillar of 29 (31.52%) femoral heads were affected. The ratio of ARCO stage III in the group with bone‐resorption lesions was significantly higher than that of the group without bone‐resorption lesions (76.09% vs 30.39%, P < 0.001).ConclusionsThis study demonstrated that the bone‐resorption lesions are mainly distributed in the lateral and central pillar of the femoral head, and the two pillars of the femoral head are usually involved by bone‐resorption lesions. Furthermore, the ratio of ARCO stage III in the group with bone‐resorption lesions was significantly higher than that of the group without bone‐resorption lesions, suggesting that the bone‐resorption lesions might accelerate the progression of ONFH.     

Validation of population‐level HIV‐1 incidence estimation by cross‐sectional incidence assays in the HPTN 071 (PopART) trial

IntroductionCross‐sectional incidence testing is used to estimate population‐level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross‐sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi‐assay algorithms (MAA) for incidence estimation to that observed in the community‐randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.MethodsHIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016–2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA‐C: LAg‐Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg‐Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.Results and discussionThe study consisted of: 15,845 HIV‐negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV‐positive participants at the 2‐year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17–1.53). Estimates of incidence were similar to observed incidence for MAA‐C, 1.26% (95% CI: 1.02–1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97–1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69–1.15, p<0.01).ConclusionsMAA‐C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.     

The effect of low‐level laser therapy on diabetic foot ulcers: A meta‐analysis of randomised controlled trials

Our purpose was to perform a meta‐analysis to evaluate the effect of Low‐level laser therapy (LLLT) on diabetic foot ulcers (DFUs). The PubMed, Cochrane, Embase, Web of Science, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases were searched systematically up to August 27, 2020. Studies that met the inclusion criteria were included in the analysis. A total of 13 randomised controlled trials (RCTs) and 413 patients were analysed. Compared with the control group, LLLT significantly increased the complete healing rate (risk ratio [RR] = 2.10, 95% confidence interval [CI] 1.56‐2.83, P < .00001), reduced the ulcer area (standardised mean difference [SMD] = 3.52, 95% CI 1.65‐5.38, P = .0002), and shortened the mean healing time (SMD = −1.40, 95% CI −1.90 to −0.91, P < .00001) of patients with DFUs. The quality of the evidence was very low according to the GRADE system. LLLT is a promising and effective adjuvant treatment to accelerate the healing of DFUs. Further evidence from larger samples and higher quality RCTs is needed to prove the effect of LLLT and to determine the most appropriate parameters for the healing of DFUs.     

A treatment protocol for chronic post‐pneumonectomy empyema associated with bronchopleural fistula: A single‐centre retrospective study

Chronic post‐pneumonectomy empyema (CPPE) associated with bronchopleural fistula (BPF) is a potentially fatal complication and remains a surgical challenge. This study aims to propose a treatment protocol for managing this severe disease. From July 2009 to June 2021, 47 CPPE with BPF patients were treated in our department. CT scan with 3D reconstruction was used to detect BPF and to evaluate the location and volume of empyema cavity. Different surgical techniques were used to close BPFs according to they sizes. Multiple pedicled muscle flaps were chosen to fill the empyema cavity, and among them, latissimus dorsi (LD) was the mostly used flap. For cases that regional flaps were not suitable, free flaps were used. Patients were followed‐up from 7.9 to 102.8 months. Forty‐four patients (93.6%) healed after the operation. Closure of BPFs failed in three patients (6.4%), leading to regional infection. These patients were treated by bronchoscopic application of sealants, continuous drainage and antibiotics, and they eventually healed. Total or partial flap loss was not seen in any of the cases. Treatment protocol was proposed based on these results. CT scan with 3D reconstruction is an effective examination to evaluate pleural cavity defect and BPF. Proper technique to close the BPF and right choice of flap to fulfil the empyema cavity are the two most important key points to treat CPPE associated with BPF patients.     

Changes in miroRNA‐103 expression in wound margin tissue are related to wound healing of diabetes foot ulcers

To investigate the relationship between small noncoding microRNA‐103 (miR‐103) and wound healing of diabetic foot ulcers (DFU) and the underlying molecular mechanism, forty type 2 diabetes mellitus with DFU (DFU group), and 20 patients with a chronic skin ulcer of lower limbs and normal glucose tolerance (SUC group) were included. Quantitative real‐time PCR method was used to determine miR‐103 expression levels in the wound margin tissue of subjects, and to analyse the relationship between the expression of miR‐103 and DFU wound healing. In vitro experiments were also performed to understand the effect of miR‐103 on the high glucose‐induced injury of normal human dermal fibroblasts (NHDFs) cells. The results showed that the miR‐103 expression level in the DFU group was significantly higher than that in the SUC group [5.81 (2.25–9.36) vs 2.08 (1.15–5.72)] (P < 0.05). The expression level of miR‐103 in the wound margin tissue of DFU was negatively correlated with the healing rate of foot ulcers after four weeks (P = 0.037). In vitro experiments revealed that miR‐103 could inhibit the proliferation and migration of NHDF cells and promote the apoptosis of NHDF cells by targeted regulation of regulator of calcineurin 1 (RCAN1) gene expression in a high glucose environment. Down‐regulation of miR‐103 could alleviate high glucose‐induced NHDF cell injury by promoting RCAN1 expression. Therefore, the increased expression of miR‐103 is involved in the functional damage of NHDF cells induced by high‐glucose conditions, which is related to poor wound healing of DFU. These research findings will provide potential targets for the diagnosis and treatment of chronic skin wounds in diabetes.     

Acceleration of differentiated service delivery for HIV treatment in sub‐Saharan Africa during COVID‐19

IntroductionIn response to COVID‐19, national ministries of health adapted HIV service delivery guidelines to ensure uninterrupted access to antiretroviral therapy (ART) and limit the frequency of contact with health facilities. In this commentary, we summarize four ways in which differentiated service delivery (DSD) for HIV treatment has been accelerated during COVID‐19 in policy and implementation in sub‐Saharan Africa (SSA) – (i) expanding eligibility for DSD for HIV treatment, (ii) extending multi‐month dispensing (MMD) and reducing the frequency of clinical consultations, (iii) emphasizing community‐based models and (iv) integrating/aligning with TB preventative therapy (TPT), non‐communicable disease (NCD) treatments and family planning commodities.DiscussionAcross SSA in 2020, countries both adapted and emphasized policies supporting DSD for HIV treatment in response to COVID‐19. Access to DSD for HIV treatment was expanded by reducing the time required on ART before eligibility and being more inclusive of specific populations including children and adolescents, pregnant and breastfeeding women and those on second‐ and third‐line regimens. Access to extended ART refills, or MMD, was accelerated across many countries. A renewed focus was given to out‐of‐facility community‐based models of ART distribution. In some settings, there was acknowledgement of the need to integrate or align other chronic medications with ART.ConclusionsAdaptations to DSD for HIV treatment in response to COVID‐19 have resulted in rapid policy change and in some cases, acceleration of implementation in SSA. As the COVID‐19 pandemic evolves, there is a critical need to assess the impact of these adaptations and, where beneficial, ensure that policies implemented in response to COVID‐19 become the new normal.     

A multi‐country cross‐sectional study to assess predictors of daily versus on‐demand oral pre‐exposure prophylaxis in youth from South Africa,Uganda and Zimbabwe

IntroductionSub‐Saharan Africa (SSA) carries the burden of the HIV epidemic, especially among adolescents and young people (AYP). Little is known about pre‐exposure prophylaxis (PrEP) uptake and preferences among AYP in SSA. We describe preferences for daily and on‐demand PrEP among AYP in South Africa, Uganda and Zimbabwe.MethodsA cross‐sectional survey was conducted in 2019 among 13‐ to 24‐year olds, capturing socio‐demographics, HIV risk behaviours and preferences for daily or on‐demand PrEP. Logistic regression models were used to estimate odds ratios, adjusting for site, sex and age.Results and discussionA total of 1330 participants from Cape Town (n = 239), Johannesburg (n = 200), Entebbe (n = 491) and Chitungwiza (n = 400) were enrolled; 673 (51%) were male, and the median age was 19 years (interquartile range 17–22 years). Of 1287 participants expressing a preference, 60% indicated a preference for on‐demand PrEP with differences by site (p < 0.001), sex (p < 0.001) and age group (p = 0.003). On‐demand PrEP was most preferred in Entebbe (75%), among males (65%) versus females (54%) and in older participants (62% in 18‐ to 24‐year‐olds vs. 47% in 13‐ to 15‐year‐olds). After adjusting for site, sex and age group, preference for on‐demand PrEP decreased as sex frequency over the past month increased (p‐trend = 0.004) and varied with the number of partners in the last 6 months, being least popular among those reporting four or more partners (p = 0.02). Participants knowing further in advance that they were likely to have sex were more likely to prefer on‐demand PrEP (p‐trend = 0.02). Participants having a larger age gap with their most recent partner and participants whose last partner was a transactional sex partner or client were both less likely to prefer on‐demand compared to daily PrEP (p = 0.05 and p = 0.09, respectively). Participants who knew their most recent partner was living with HIV or who did not know the HIV status of their most recent partner were less likely to prefer on‐demand PrEP (p = 0.05).ConclusionsOur data show that AYP in four SSA communities prefer on‐demand over daily PrEP options, with differences seen by site, age and sex. PrEP demand creation needs to be reviewed, optimized and tailored to socio‐demographic differences and designed in conjunction with AYP.