Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Effect of Genistein Intake on Some Cardiovascular Risk Factors: An Updated Systematic Review and Meta-analysis

Genistein, an isoflavone in soybean products has potential cardio-protective effects and is used also as an alternative for estrogen therapy in postmenopausal women. However, results in this regard are inconsistent and also, not all risk factors related to cardiovascular supportive effects have been meta-analyzed. We searched PubMed, Scopus, ISI Web of Science, and Google Scholar from inception up to October 2020. Random-effects meta-analysis was used for data synthesis. The search included studies with information on genistein supplementation and lipid profile [triglycerides (TG), total cholesterol (TC),low-density lipoprotein (LDL-C), and high-density lipoprotein HDL-C)], systolic and diastolic blood pressure (SBP & DBP), body mass index [BMI] and body weight. Pooled results of studies showed that genistein intake significantly reduced TC [95%CI: -0.49(-0.80, -0.18); P=0.002)], LDL-C [95%CI: -0.60(-1.10, -0.10); P=0.018)] and SBP [95%CI: -0.52(-0.90, -0.14); P=0.007)]. DBP, HLD-C, TG, BMI, and body weight showed no meaningful improvement. Subgroup analysis showed that LDL-C and SBP were reduced more effectively in postmenopausal women with metabolic syndrome. Genistein intake more than 6 months showed a greater effect on lowering cholesterol -0.76(-1.27, -0.24), SBP [-0.39(-0.70, -0.08)] and DBP -0.40(-0.81, -0.00) and increasing TG and LDL-C. This meta-analysis provides consistent evidence that genistein intake reduces the CVD risk factors of TC, LDL-C, and SBP significantly.     

Subtalar Joint Distraction Arthrodesis Utilizing a Titanium Truss: A Case Series

Subtalar joint distraction arthrodesis has been recommended for the treatment of conditions such as nonunion or malunion of subtalar joint arthrodesis posttraumatic arthritis. Both conditions are difficult to treat, because the deformities created in the frontal and sagittal planes of these conditions are complex. If these malalignments are not addressed, ankle joint instability and wear occur over time. In general, either autograft or allograft bone has been used to perform distraction arthrodesis of the subtalar joint. Although studies have shown successful use, there have been complications. Autografts have resulted in donor site morbidity and limitations on graft size, and allografts have shown high nonunion rates. Both autografts and allografts have shown graft collapse over time. Recent literature has discussed the use of tantalum technology to span large defects in bone healing. Studies have shown that tantalum provides superior strength and bone incorporation compared with autografts and allografts. This case series presents 2 cases in which tantalum truss technology was used for distraction arthrodesis. Although this series is limited in patient numbers, both cases show effective graft incorporation with no loss in height over time and earlier return to activity compared with previous studies that used autograft and allograft wedges.     

Effects of Hallux Valgus Surgery on Balance and Gait in Middle Aged and Older Adults

Hallux valgus is associated with balance deficits, and has been implicated as an independent risk factor for falls in older adults. However, it is unknown what effect hallux valgus surgery has on static and dynamic (i.e., while walking) balance in older adults. We enrolled 13 middle-aged and older aged adults (mean age 54.3 ± 12.7 years, range 47 to 70) who underwent isolated hallux valgus surgery and followed them for 12 months. Preoperative and postoperative gait and balance performance was assessed using non-invasive body worn sensors with standardized and validated testing protocols. Visual analog scale (VAS) for pain and radiographic angles were also assessed. All subjects reported improvements in pain (VAS mean change -38.3 ± 10.3 mm), and all subjects demonstrated improvements in their hallux valgus angles and first/second intermetatarsal angles (mean change 16.3 ± 8.8°, and 5.5 ± 3.0°, respectively). While standing in full tandem, center of mass (COM) sway was improved upon by 59% at 1 year postoperative (p < .05, paired t-test). While most gait parameters demonstrated little change postoperatively, patients tended to spend less time in double support (p = .08, paired t-test), while gait variability increased by 55% (p = .03, paired t-test) and medial-lateral sway while walking increased by 43% (p = .08, paired t-test) 12 months postoperatively. Balance improved after hallux valgus surgery in our population, particularly when subjects were forced to rely on their operative foot for support (e.g., full tandem). Patients also seemed to walk with greater variability in stride velocity and with greater medial-lateral sway postoperatively, suggesting perhaps increased ambulatory confidence after successful hallux valgus surgery.     

Replantation and Lengthening of a Lower Leg in a 7-Year-Old Child: A Case Report

Replantation of the lower leg has controversial indications, but it may be considered in carefully selected patients. Although the function of prosthetic lower legs has been improved in recent decades, leg salvage remains a laudable goal. We present the case of a 7-year-old child who sustained a traumatic amputation at the level of the middle tibia with loss of the middle portion of the lower leg. We performed successful replantation, and tibia lengthening was performed starting 10 days after replantation and lasted 6 months.     

Clinical Effectiveness of Treatment Strategies for Prosthetic Joint Infection Following Total Ankle Replacement: A Systematic Review and Meta-analysis

Prosthetic joint infection (PJI) after total ankle replacement (TAR) is a challenging complication, which often requires debridement and implant retention (DAIR) with or without polyethylene exchange, revision surgery, implantation of a cement spacer, conversion to arthrodesis, or even amputation. The optimum treatment for ankle PJI is not well established. We conducted a systematic review and meta-analysis to compare the clinical effectiveness of various treatment strategies for infected ankle prostheses. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library up to December 2018 for studies evaluating the impact of treatment in patient populations with infected ankle prostheses following TAR. Binary data were pooled after arcsine transformation. Six citations comprising 17 observational design comparisons were included. The reinfection rates (95% confidence intervals) for DAIR with or without polyethylene exchange, 1-stage revision, 2-stage revision, cement spacer, and arthrodesis were 39.8% (24.4 to 56.1), 0.0% (0.0 to 78.7), 0.0% (0.0 to 8.5), 0.2% (0.0 to 17.9), and 13.6% (0.0 to 45.8), respectively. Rates of amputation for DAIR with or without polyethylene exchange and cement spacer were 5.6% (0.0 to 16.9) and 22.2% (6.3 to 54.7), respectively. Measures of function, pain, and satisfaction could not be compared because of limited data. One- and 2-stage revision strategies seem to be associated with the lowest reinfection rates, but these findings are based on limited data. Arthrodesis and DAIR with or without polyethylene exchange appear to be commonly used in treating infected ankle prosthesis, but are associated with poor infection control. Clear gaps exist in the literature, and further research is warranted to evaluate treatment strategies for infected ankle prosthesis.     

Dietary and herbal supplements use among patients hospitalized in internal medicine departments

ObjectivesTo assess consumption of dietary and herbal supplements (DHS) among patients in internal medicine departments and determine whether such use is documented in their medical files.Methods267 patients from three internal medicine departments of an academic medical center in Haifa, Israel were assessed prospectively with questionnaires about their DHS use in the month preceding hospitalization. DHS were categorized into vitamins & minerals, herbal supplements and others. Further data was then collected from patients' medical records on socio-demographic and medical characteristics, as well as documentation of DHS use.Results123 patients (50.6 %) used DHS on a daily basis. Most of them (53.7 %) were using more than one DHS. DHS use was more prevalent in older (OR = 1.02 [1.001–1.036], p = 0.034) and educated (OR = 0.482 [0.252-0.923], p = 0.028) patients. Vitamins & minerals were used mainly to enhance vitality and address laboratory abnormalities, whereas herbal supplements were used mainly for gastrointestinal problems (p < 0.001). DHS use was reported to the physicians by 42 % of the patients, mostly at the patients’ initiative [92 (82.1 %), p < 0.001)]. Vitamins and minerals were the most reported category of DHS (94 (57.3 %), p < 0.001). The use of DHS was reported to physicians for 112 DHS (41.8 %) but only 32 DHS (11.9 %) were documented in their medical files. The documentation of vitamins and minerals was significantly higher compared to herbal supplements documentation (29 (17.7 %) & 3 (2.9 %) respectively, P < 0.001).ConclusionsDHS are commonly used by patients hospitalized in the internal medicine departments. Many patients do not report such use to the physicians, and more strikingly, physicians do not document DHS use in patient medical files. This communication gap may have serious medico-legal ramifications due to DHS side effects and DHS interactions with other DHS and with conventional drugs.