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Neurofibromatosis (NF) is an inherited neuroectodermal abnormality that primarily affects the growth of neural tissues, and Riccardi classified it into eight types. Segmental neurofibromatosis, which is a rare form of neurofibromatosis, is classified as type 5. We report a case for very unusual presentation of segmental NF with unilateral lisch nodules and uncommon sites involving the scalp. Moreover, we could find only one case report of segmental NF with lisch nodules in the literature and could not find any case report involving the scalp.

Management of an uncorrected broncho-oesophageal fistula in the perioperative period is a challenge for the anaesthesiologist. Positive pressure ventilation which is inevitable during surgery will lead to gastric insufflation and there is a high risk of aspiration of gastric contents. In this case report, we discuss how we used a double lumen tube to occlude a pericarinal broncho-oesophageal fistula. This method was quite effective as it obviated the need for isolating the lung as well as ensured smooth delivery of positive pressure ventilation during the surgery.

SummaryAfrican populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multigenerational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within the African continent, as well as how within-Africa variation can be informative for broader variant interpretation; many variants appearing rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity within Africa.

BACKGROUND Chronic hepatitis B (CHB) infection remains a significant public health issue for Indigenous Australians, in particular for remote communities. AIM This study aimed to evaluate the spectrum of hepatitis B virus (HBV) care provided to a remote Aboriginal community. Measures studied included screening, seroprevalence, vaccination rates and efficacy, and HCC risk and surveillance adherence. METHODS A retrospective audit of HBV care received by all permanent residents currently attending a remote Aboriginal Health service. This study was endorsed by both the local Aboriginal Health service and the Aboriginal Health Council of South Australia. RESULTS A total of 208 patients attended the clinic, of whom 52% (109) were screened for HBV. Of these, 12% (13) had CHB and 20% (22) had evidence of past infection. Similarly, of the 208 attending patients, complete vaccination was documented in 48% (99). Of the 33 patients with post-vaccination serology, 24% (8) had sub-therapeutic (

BACKGROUND AND AIMS: Recently, there has been a considerable increase in patients with nonalcoholic fatty liver disease. Availability of high-efficacy drugs for hepatitis B and hepatitis C virus (HCV) infection may have changed the disease prevalence. We aimed to study the impact of this changing epidemiology in patients undergoing liver transplantation (LT) over a 10-year period. METHODS: The study population was stratified into Period 1 (2009–2014) and Period 2 (2015–2019). Demographics, indications for LT and changes in the epidemiology between two periods were analysed. Aetiology-based posttransplant survival analysis was carried out. RESULTS: Indication for LT among 1017 adult patients (277 in Period 1 and 740 in Period 2) showed a significant increase in nonalcoholic steatohepatitis (NASH; 85 [30.7%] and 311 [42%]; P = 0.001), decrease in hepatitis C (49 [17.7%] and 75 [10.1%]; P = 0.002), and increase in hepatocellular carcinoma from Period 1 to Period 2 (13 [26.5%] to 38 [50.7%]; P = 0.009) among HCV patients. Patients transplanted for NASH had a lower 5-year survival compared with viral hepatitis (75.9% vs 87.4%; P = 0.03). There was a strong association between coronary artery disease and NASH (hazard ratio = 1.963, 95% confidence interval, 1.19–3.22). CONCLUSION: NASH is the leading indication for liver transplantation in India, surpassing viral hepatitis in recent years.

A 66-year-old man, diabetic, hypertensive and dyslipidaemia, presented with gradual onset of blurring of vision in both eyes (OU) since past 3 months. The best corrected visual acuity (BCVA) at presentation was 20/200 in right eye (OD) and 20/160 in left eye (OS). While, the anterior segment

Background Technical errors are the most common preventable cause of recurrence after high ligation and stripping procedures for the treatment of great saphenous vein incompetence. Ultrasound-assisted varicose vein surgery (UAVS) uses intraoperative ultrasound during high ligation and stripping to minimize such failures, although no data have been reported regarding its use during open surgery. The present study compared the short-term outcomes of UAVS and endovenous laser ablation (EVLA) with a 1470-nm laser. Methods The present prospective randomized study was conducted from January 2019 to December 2019. We compared 40 patients who had undergone UAVS under regional anesthesia with an equal number of patients who had undergone EVLA under tumescent anesthesia. Both groups received 1 week of standardized postoperative analgesia. The improvements in the pain score, venous clinical severity score, and recurrence at 6 months and 1 year were studied. Results No significant differences were found in either clinical or radiologic great saphenous vein recurrence after UAVS compared with EVLA at 1 year. The mean pain score at 8 hours after the procedure was higher in the UAVS group (3.7 ± 1.2 vs 2.9 ± 1.0; P = .03). At 1 week, the score was higher in the EVLA group (1.8 ± 0.7 vs 1.4 ± 0.5; P = .01). At 6 months, the venous clinical severity score had improved from 9.2 ± 3.7 to 2.4 ± 1.4 in the UAVS group and from 9.3 ± 3.2 to 2.1 ± 0.8 in the EVLA group (P = .64). At 1 year, the corresponding scores were 1.3 ± 0.7 and 1.4 ± 0.6 (P = .21). Conclusions UAVS has high technical success, making it a suitable alternative to EVLA using a 1470-nm laser.

INTRODUCTION Safely increasing organ donation to meet need is a priority. Potential donors may be declined due to perceived blood borne virus (BBV) transmission risk. With hepatitis C (HCV) curative therapy, more potential donors may now be suitable. We sought to describe potential deceased donors with increased BBV transmission risk. METHODS We conducted a cohort study of all potential organ donors referred in New South Wales, Australia, 2010-2018. We compared baseline risk potential donors to potential donors with increased BBV transmission risk, due to history of HIV, HCV or hepatitis B and/or behavioural risk factors. RESULTS There were 624/5749 potential donors (10.9%) perceived to have increased BBV transmission risk. This included 298/5749 (5.2%) with HCV (including HBV co-infections) and 239/5749 (4.2%) with increased risk behaviours (no known BBV). Potential donors with HCV and those with increased risk behaviours were younger and had fewer comorbidities than baseline risk potential donors (p

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

A 75-year-old man was initially admitted for elective inguinal hernia repair but was noted by the anaesthetist to have a ‘uvula-like’ mass in the oropharynx arising inferiorly, either from the base of the tongue or supraglottis, as seen in [figure 1][1]. He denied difficulties in swallowing

Study the changing clinical and therapeutic profiles of type 2 diabetes (T2D) patients during a 10-year period in a diabetes care centre in Southern India.Retrospective, cross-sectional data of newly registered and review patients at four periods between 2009 and 2018 were analysed (n = 50,322). Clinical findings, anthropometry, blood pressure (BP), glycaemia, lipids, treatment, and co-morbid conditions were analysed. We studied the trends in age and gender distributions, body mass index (BMI), glycaemia, (Glycosylated haemoglobin A1c (HbA1c) levels), BP, cholesterol, triglycerides and therapeutic regimen during this period. Trend analyses were done.Approximately 60% of patients were men. Percentages in 30-40 years increased, ∼60% were aged 50-69 years and proportion of older patients decreased (p 0.0001). In 10 years, 85.9% was overweight, obesity increased from 22.1% to 25.0% (p 0.0001) and13% maintained normal BMI. HbA1c7.0% remained approximately at 22%, percentage with moderate glycaemic control (HbA1c 7.0-7.9%) increased significantly, HbA1c of ≥9.0% decreased from 35.1% to 29.1% (p 0.0001). Use of monotherapy decreased. Prevalence of hypertension increased from 16.2% to 21.6% (p 0.0001); use of Angiotensin Receptor Blockers (ARB) and calcium channel blockers increased, Angiotensin Converting Enzyme Inhibitors and thiazides decreased (p 0.0001). Increased use of statins paralleled with reduction in total cholesterol and LDLc.Increasing percentages of younger patients and obesity, use of multiple drugs and reduction in HbA1c were the important observations. Rising prevalence of hypertension, increased use of ARB and statins with better control of dyslipidaemia was observed. Achievement of ideal HbA1c and BP were suboptimal.

To investigate the effects of iontophoresis–ultraviolet A (UVA) cross-linking (CXL) with hypotonic riboflavin solution on the ultrastructural changes in the lamellae, collagen fibrils (CFs), and proteoglycans (PGs) in the central and peripheral stroma of the human corneal buttons. The iontophoresis method was used for the trans-epithelial application of hypotonic riboflavin in ex vivo corneal culture for 5 min. The corneas were irradiated using three methods: Group 1 (G1), a UVA irradiance of 3 mW/cm2 for 30 min; Group 2 (G2), a UVA irradiance of 10 mW/cm2 for 9 min; Group 3 (G3), without UVA irradiation. Three untreated corneas were used as controls (G0). After the CXL procedure, the corneas were processed for electron microscopy. The CF diameter and PGs in each sample were analyzed using the iTEM program. The keratocyte organelles and stromal architecture in the peripheral cornea were better preserved than those in the central cornea. In G1 and G2, the mean CF diameter in the peripheral cornea was significantly higher than that in the central cornea. In G3, the CF diameter in the central cornea was significantly larger than that in the peripheral cornea. Furthermore, differences in PG area size were observed between the central and peripheral corneas in all groups. Riboflavin + UVA application at 3 mW/cm2 for 30 min and 10 mW/cm2 for 9 min was a suitable method of CXL; however, 3 mW/cm2 for 30 min improved the organization and size of the collagen fibrils. CXL treatment applied at the periphery was more effective than that applied at the center.

OBJECTIVE Liver cirrhosis is a chronic disease complicated by recurrent hospital admissions. Self-management skills could facilitate optimal disease management. Currently there is no validated instrument for measuring self-management in these patients. Hence, we evaluated the internal reliability and construct validity of the Partners in Health (PIH) scale, a chronic condition self-management tool in cirrhotic patients. METHODS In this prospective cohort study, the PIH scale was administered to 133 consenting patients within a Chronic Liver Failure Program of a tertiary hospital from February 2017 to May 2018. A Bayesian confirmatory factor analysis (BCFA) was used to evaluate an a priori 4-factor structure. Omega coefficients and 95% credible intervals (CrI) were used to assess internal reliability. Known-group validity was assessed in patients receiving active case management (n = 60) versus those without (n = 73). RESULTS The mean (± standard deviation; SD) age of the participants was 62 (±11) years. Model fit for the hypothesised model was adequate (posterior predictive p-value = 0.073) and all hypothesised factor loadings were substantial (>0.6) and significant (p

BACKGROUND AND AIMS India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P

Background In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV. Methods Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems. Results There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group. Conclusion In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality. Registration number CTRI/2018/11/016315 (www.ctri.nic.in).

Background International Federation of Gynaecology and Obstetrics (FIGO) staging of carcinoma cervix, although essentially clinical, acknowledges the benefits of MRI. The impact of incorporating MRI in staging of cervical cancer and the discordance between clinical-and MRI-based FIGO staging is not well studied, especially in low- and middle-income countries. Aim We aim to study the role and accuracy of MRI in staging carcinoma cervix, its correlation with clinical FIGO and histopathological staging with emphasis on how it can change treatment plan. Methods Retrospective observational cohort study (n = 193) where MRI details of different staging parameters of the study subjects were compared with clinical FIGO staging and histopathology to assess correlation and agreement between them. Change of clinical FIGO stage and hence treatment plan brought about by incorporating MRI was assessed. Results MRI had a tumor detection rate of 94.3%, overall staging accuracy of 78.3% and very strong correlation with histopathology (Spearman's coefficient of rank correlation, r = 0.886). Clinical FIGO and MRI had agreement only in 52.8% cases (r = 0.61). Incorporating MRI changed the clinical stage in 47.2% patients and subsequently modified primary treatment plan in 23.3%. Conclusion MRI is highly accurate in evaluating carcinoma cervix and has good correlation with histopathology. Our data shows low agreement between MRI and clinical FIGO staging. Thus, incorporating MRI in FIGO staging has considerable impact in altering treatment decisions and should be offered to all patients for staging carcinoma cervix.

Introduction: Renal dysfunction at presentation is uncommon in primary membranous nephropathy (PMN). The data on the outcome of PMN patients with renal dysfunction at outset are scarce. The objective of the current study was to report the clinical outcomes of PMN patients with renal dysfunction. Material and Methods: This prospective longitudinal observational study included PMN patients (both incident and treatment resistant) with an estimated glomerular filtration rate of 2. Immunosuppressive treatment was as per the unit’s protocol. Patients were evaluated for proteinuria, creatinine, and serum albumin at monthly intervals for 6 months, then quarterly for a year, and then biannually. Both serum and tissue anti-PLA2R were performed at baseline. Outcome: Percentage of patients achieving clinical remission. Results: Sixty-four adults met study criteria and were analysed. The median (IQR) age of the patients was 48 (40, 56) years. PMN was PLA2R related in 52 (81.3%) patients. Twenty-eight (43.8%) and 30 (46.9%) patients were in remission at 12 months and at the end of the study [median (IQR) follow up: 24 months (12, 35)], respectively. Eight (12.5%) had progressed to end-stage renal disease at the last follow-up. Median (IQR) baseline anti-PLA2R titre was 150.1 RU/mL (38.5, 308). Nineteen (61.3%) and 18 (58.1%) patients with >90% reduction in anti-PLA2R titres at 12 months were in clinical remission at 12 months and at the end of the follow-up, respectively. Both cyclical cyclophosphamide/steroids (cCYC/GC) and rituximab were equally effective in inducing remission, but rituximab had a favourable adverse event profile compared to cCYC/GC. Conclusion: To conclude, both cCYC/GC and rituximab are equally effective in inducing remission of nephrotic state with compromised renal function due to PMN. Immunosuppression induces remission in up to 50% PMN patients with CKD-stage 3–4.

Aging is associated with an increased prevalence of subclinical atherosclerosis and stiffening of the arterial walls (arteriosclerosis). These 2 coexisting conditions are mitigated by the presence of ideal cardiovascular health (optimal levels of fasting blood glucose, cholesterol, resting blood pressure, body mass index, no smoking, good dietary quality, and regular physical activity). We hypothesized that the concomitant presence of subclinical atherosclerosis (coronary artery calcification), arteriosclerosis (higher carotid-femoral pulse wave velocity), and suboptimal cardiovascular health is associated with increased risk of cardiovascular disease relative to the absence of these 3 conditions. We tested our hypothesis in the community-based Framingham Heart Study cohort (N=2580, mean age 52 years, 49% women). We classified participants based on (1) the presence versus absence of coronary artery calcium; (2) higher (>sex-specific median) carotid-femoral pulse wave velocity; (3) poor cardiovascular health (score 0–7). Thus, participants could have no abnormalities (referent group), 1, 2, or 3 suboptimal measures. We used Cox regression to relate the number of suboptimal measures (0–3) to the incidence of cardiovascular disease during follow-up (median 14 years). Cardiovascular disease incidence rates/1000 person-years in groups with 0 to 3 suboptimal measures were 1.93 (95% CI, 1.28–2.90), 4.68 (95% CI, 3.48–6.29), 8.93 (95% CI, 6.99–11.41), and 18.26 (95% CI, 14.65–22.77), respectively. Compared with the group with no abnormalities, corresponding multivariable-adjusted hazards ratios for cardiovascular disease were 1.81, 2.18, and 3.71, respectively ( P

Copyright © Richard C. Strange et al., 2021. Objective: Testosterone therapy (TTh) may reduce morbidity/mortality in men with adult-onset testosterone deficiency (TD), though some cardiovascular safety concerns remain. Increased hematocrit (HCT), a recognized effect of therapy, may be associated with cardiovascular disease and mortality. We examined HCT change (Δ) in men prescribed/not prescribed testosterone, and associations with mortality. Methods: We analyzed data from a prospective registry study with adult-onset TD patients: 353 men given testosterone undecanoate (TU) and 384 opting against TTh. Change in HCT after 12, 48, 72, and 96 months of TU and at final assessment was compared (nonparametric tests). The association between baseline HCT, ΔHCT, and mortality was studied using logistic and Cox regression. Results: HCT increased significantly (median change at final assessment: +5.0%) in men on TTh. HCT was higher (p = 0.021, rank-sum test) in those alive than in those who died, although median values were identical (49.0%). Baseline HCT and ΔHCT were inversely associated with mortality after adjustment for age in both logistic and Cox regression models. Men with final HCT >49.0% (median) suffered lower mortality than men with HCT ≤49.0%. Conclusions: A median HCT increase of 5.0% was associated with TTh, mostly within 48 months of commencing therapy. An increase in HCT (up to 52.0% at final assessment) was independently associated with reduced mortality, indicating current guidelines using a HCT value of 54.0% as a threshold for management change are appropriate until further study. No funding was received for this article.

Objectives: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control. Background: The sex-specific epidemiology of AF in HF is sparse. Methods: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018. Results: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability–weighted models across all strata and in both sexes (hazard ratio: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03). Conclusions: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.

Background & aims A unique model of care was adopted in Australia following introduction of universal subsidised direct-acting antiviral (DAA) access in 2016 in order to encourage rapid scale-up of treatment. Community-based medical practitioners and integrated hepatitis nurses initiated DAA treatment with remote hepatitis specialist approval of the planned treatment without physical review. We aimed to evaluate outcomes of community-based treatment of hepatitis C (HCV) through this remote consultation process in the first 12 months of this model of care. Methods A retrospective chart review of patients undergoing community-based HCV treatment from general practitioners and integrated hepatitis nurse consultants through the remote consultation model in three state jurisdictions in Australia from 1 March 2016 to 28 February 2017. Results SVR12 was confirmed in 383/588 (65.1%) subjects intended for treatment with a median follow-up time of 12 months (IQR 9-14 months). The SVR12 test was not performed in 159/588 (27.0%) and 307/588 (52.2%) did not have liver biochemistry rechecked following treatment. Subjects who completed follow-up exhibited high SVR12 rates (383/392,97.7%). Nurse-led treatment was associated with higher confirmation of SVR12 (73.7% v 62.4%, p = 0.01) and liver biochemistry testing post treatment (57.5% v 45.0%, p = 0.01). Conclusions Community-based management of HCV through remote specialist consultation may be an effective model of care. Failure to check SVR12, recheck liver biochemistry and appropriate surveillance in patients with cirrhosis may emerge as significant issues requiring further support, education and refinement of the model to maximise effectiveness of future elimination efforts. This article is protected by copyright. All rights reserved.

Recent advances in gene therapies offer novel therapeutic options for many diseases that are otherwise resistant to pharmacologic treatment. Through gene therapy, scientists now have the opportunity to replace disease-causing genes with healthy copies, inactivate genes functioning improperly and introduce genes into the body to help fight disease.1 As of 31 December 2020, the US Food and Drug Administration (FDA) has approved five gene therapies, and more than 900 are in clinical development.2 Based on an assessment of the current pipeline, the FDA predicts it will approve 10–20 gene therapy products per year by 2025.3 In anticipation of many more approvals in the coming years, the FDA recently released final guidance documents on the clinical development and manufacturing of gene therapy products.2 To facilitate the development of these therapies, the 21st Century Cures Act introduced a new expedited development programme, the regenerative medicine advanced therapy (RMAT) designation. This programme grants all the benefits of the breakthrough therapy designation, including rolling review and intensive FDA guidance on efficient drug development, along with an expanded range of options to fulfil postapproval commitments.4 As of 31 December 2020, the FDA has granted RMAT designation to 58 products.5 Although many laud these novel gene therapies as clinically transformative, there is growing concern about the high cost of these products, with list prices for one-time infusions ranging from $373 000 to as much as $2.1 million.6 In addition, gene therapies have been associated with serious safety risks including life-threatening immune responses and insertional mutagenesis-induced malignancies.7 As more gene therapies begin to enter the market, understanding the FDA’s past practices and standards in their review and approval of these products will help inform future regulatory decision-making, particularly upcoming approvals through the RMAT pathway, reimbursement decisions of payors, and the clinical …

Background Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression. Methods We investigated the relationship between urine biomarkers of kidney tubular health (EGF and α-1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m2. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period. Results Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and α-1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression. Conclusions After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and α-1 microglobulin concentrations were each associated with CKD progression in children.

Introduction Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known. Methods We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system–resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years. Results At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy. Conclusions To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN., Graphical abstract

Inhaled corticosteroids (ICS) have a central role in the management of obstructive airway diseases. Use of ICS in asthma and chronic obstructive pulmonary disease (COPD) is associated with a small but clear increase in incidence of pneumonia and tuberculosis. Since ICS use in obstructive airway diseases has beneficial effects with regard to symptoms, lung function, quality of life and exacerbations, denying the benefit of ICS solely based on this small elevated risk of pneumonias and tuberculosis is not justified. The present article attempts to elucidate mechanisms contributing to the increased risk, assesses the magnitude and risk factors of tuberculosis in patients using ICS and provides practical suggestions for practising clinicians.

Background Cognitive decline is a non-hemorrhagic, major complication of intracranial dural arteriovenous fistula (DAVF), thought to be primarily related to venous hypertension. However, imaging features to predict cognitive decline are scanty in the literature. Purpose To evaluate functional connectivity (FC) changes of resting-state networks (RSNs) in DAVF before and after treatment and its relation to cognitive impairment. Study type Prospective. Subjects DAVF subjects were screened for inclusion. Pre-embolization (N = 33, mean age 45.9 years, 29 males), 1 month post-embolization (N = 20, mean age 42.7 years, 19 males), and healthy controls (HC, N = 33, mean age 45.09 years, 27 males). Field strength/sequence 3.0 T, resting-state functional magnetic resonance imaging (MRI), three-dimensional (3D) T1, T2 fast spin echo (FSE), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), fluid-attenuated inversion recovery, and time of flight. Assessment Data quality assessment was performed. FC analysis was done using group independent component analysis (ICA) and seed to voxel analysis. Neuropsychology (NP) scores of patients were compared with HC and correlated with FC changes. Statistical tests Voxel-wise parametric T-statistics for F-test was executed in FC analysis (p-FDR corrected Results Both RSNs analysis methods showed reduced FC at the precuneus-posterior cingulate cortex (PC-PCC) of default mode network (DMN), anterior cingulate cortex (ACC) of the salience network (SN), and possible compensatory increased connectivity at the frontoparietal (FPN) and dorsal attention (DAN) networks. DAVF with low NP scores showed reduced FC at DMN and SN and minimal to absent connectivity at FPN and DAN. At post-embolization 1-month follow-up, improvement in FC at PC-PCC of DMN and ACC of SN were noted. Data conclusion RS-fMRI in DAVF displayed FC changes that may be related to cognitive decline and its subsequent reversibility after treatment. FC changes at DMN, SN, FPN, and DAN were linked to cognitive decline and the corresponding NP scores. Level of evidence 2 TECHNICAL EFFICACY: Stage 2.

Background Junctional kyphosis (JK) is usually observed in long-level instrumented fusion surgeries. Various contributing factors are proposed, the pre-existing and postoperative spinal imbalance is considered as the single most important factor for the development of JK in adult spinal deformity surgeries. Distal JK (DJK) is seldom reported compared to proximal JK (PJK), and scarce literature exists. Methods We report 2 unique cases of distal junctional failure (DJF) with worsening of neurology, secondary to nontraumatic fracture of a lower instrumented vertebra operated for thoracic canal stenosis without deformity. The first case had acute worsening of the Neurology during follow up and on evaluation, the supine CT and MRI scan revealed well decompressed spinal canal, no implant migration to the canal, no screw loosening, or rod failure. Supine sitting radiographs demonstrated DJK with Fracture and the patient underwent extension of fusion till the pelvis with 3-rod construct and interbody fusion, because of the instability at the L1 level. The second case remained neurologically stable for a month and then had an acute onset of back pain, sensory deficit, and urine incontinence. The supine-sitting dynamic radiograph done demonstrated L1 fracture with DJK at D12–L1 levels. The patient was counseled for extension of fusion, which was deferred by the patient. Results Patients in our series, had an acute worsening of neurological deficit within a month of posterior spinal fixation. Their supine imaging was almost normal, and the diagnosis of DJK with L1 fracture instability was possible only on a supine-sitting dynamic radiograph. Various factors like obesity, TL kyphosis, osteoporosis, etc. can be the attributing factors for the development of DJK Conclusion A high index of suspicion is required for diagnosing nontraumatic fracture in long-level fusion patients with acute neurological worsening. The supine-sitting dynamic radiograph is an important diagnostic tool for DJF in patients having difficulty standing erect. Level of Evidence 4. Clinical Relevance Application of sitting and supine dynamic radiographs to diagnose instability in patients unable to stand for flexion and extension radiographs.

BACKGROUND The standard conventional radiation schedule for early laryngeal cancer is 64 - 70 Gy in 2 Gy per fraction over 6.5 - 7 weeks. Hypofractionated radiotherapy in early laryngeal cancer allows delivery of larger dose per fraction (fraction size) in decreased overall treatment time with improved local control and similar survival rates. Reduction in treatment time also optimizes the usage of radiotherapy resources. The purpose of this study was to estimate the local control rates, survival rates and toxicity profile of hypofractionated radiotherapy of 52.5 Gy in 15 fractions for early glottic cancer. METHODS Twenty-eight patients with early glottic squamous cell carcinoma (SCC) treated with hypofractionated definitive radiotherapy from June 2015 to December 2019 were analyzed. The median age was 61 years. Total dose of 52.5 Gy in 15 fractions was delivered over three-four weeks with a fraction size of 3.5 Gy. The median follow-up period was 23.8 months. RESULTS The 5-year local control rates were 96.4 % with one recurrence. The 5-year overall survival rate was 100 % and cause specific survival at 5 years was 100 %. There was no association of T1 sub staging, T2 (P - 0.40) and no significant association of anterior commissure involvement (P = 0.408, chi square value = 3.982) and pretreatment haemoglobin (P - 0.480) on local control. Late complications include laryngeal oedema (21.5 %), altered thyroid function (3.6 %), cardiac complication (3.6 %) and altered voice quality (14.3 %).There was no association of local control with field size (FS) (P = 0.812), beam energy (P = 0.098 ) overall treatment time of less than thirty days (P - 0.747). CONCLUSIONS Local control with hypofractionated radiotherapy for early laryngeal glottis squamous cell carcinoma is excellent with no severe complications. The short overall treatment time enables channelling of radiotherapy resources in low budget countries with long wait list for radiation. KEYWORDS Early Laryngeal Cancer, Glottic Cancer, Hypofractionated Radiotherapy, Overall Treatment Time.

Background: The background of the work stems from the observation due to the prevalence of antipsychotic drugs in causing metabolic disorder. The metabolic disorder is one of the major concern of antipsychotic drugs for schizophrenic patients. The present study is mainly aimed to establish the role of haloperidol and risperidone or olanzapine in causing metabolic syndrome of schizophrenic patients. Methods: Sixty-four schizophrenic patients were divided into two groups. First and second group received haloperidol and risperidone or olanzapine respectively for three months. Body mass index, random blood sugar and lipid profile were investigated before and after the treatment. Results: Both groups of schizophrenic patients have shown a significant increase in the BMI, random blood sugar and lipid profile indicating a propensity to cause metabolic disorder. Conclusion: From the present study it is concluded that there is a high prevalence of metabolic disorder those who received antipsychotic drugs like haloperidol and risperidone or olanzapine.

Background Intravenous fluid optimization is an essential component of managing patients in a critical care setting. A cumulative positive fluid balance is consistent with poor outcomes in patients admitted to the intensive care unit (ICU). The overall utility of net cumulative fluid balance as a surrogate for assessing fluid overload has been interrogated. Materials and methods This study was a prospective single-center observational study, which was done to correlate body weight changes with fluid balance in ICU patients and evaluate its impact on clinical outcomes. Inclusion criteria consisted of adult patients who were admitted to the critical care unit on specialized beds with integrated weighing scales between September 2017 and December 2018. The evaluation of the effect of changes in body weight on ICU survival was the primary objective of the study. Results We enrolled 105 patients in this study. The ICU mortality was 23.80% with non-survivors showing more weight gain than the survivors. Statistically significant weight gain was documented in the non-survivors on days 3 and 4 (1.9 vs 1.05; p = 0.0084 and 2.6 vs 1.6; p = 0.0030) of ICU admission. Non-survivors had greater cumulative positive fluid balance on fourth, fifth, and sixth days post-ICU admission when compared to survivors (3586 vs 1659 mL, p = 0.0322; 5418 vs 1255 mL, p = 0.0017; and 5430 vs 2305 mL p = 0.0264, respectively). In multivariate regression analysis, cumulative fluid balance did not correlate with days on mechanical ventilation or length of stay in ICU. Changes in body weight and cumulative fluid balance showed a good correlation. Conclusion In patients admitted to the ICU, weight gain on third and fourth days of admission is concordant with increased ICU mortality. Body weight changes were seen to correlate well with the cumulative fluid balance. How to cite this article Mishra RK, Pande A, Ramachandran R, Trikha A, Singh PM, Rewari V. Effect of Change in Body Weight on Clinical Outcomes in Critically Ill Patients. Indian J Crit Care Med 2021;25(9):1042–1048.

Background and Purpose: Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants. Methods: Using a fingertip PAT device, we assessed pulse amplitude in Framingham Offspring and Third Generation participants (n=3865; mean age, 55±14 years; 52% women) at baseline and in 30-second intervals for 4 minutes during reactive hyperemia. The PAT ratio (relative hyperemia index) was calculated as the post-to-pre occlusion pulse signal ratio in the occluded arm, relative to the same ratio in the control (nonoccluded) arm, and corrected for baseline vascular tone. Baseline pulse amplitude and PAT ratio during hyperemia are measures of pressure pulsatility and microvascular function in the finger, respectively. We used Cox proportional hazards regression to relate PAT measures in the fingertip to incident CVD events. Results: During follow-up (median, 9.2 years; range, 0.04–10.0 years), 270 participants (7%) experienced new-onset CVD events (n=270). In multivariable models adjusted for cardiovascular risk factors, baseline pulse amplitude (hazard ratio [HR] per 1 SD, 1.04 [95% CI, 0.90–1.21]; P =0.57) and PAT ratio (HR, 0.95 [95% CI, 0.84–1.08]; P =0.43) were not significantly related to incident composite CVD events, including myocardial infarction or heart failure. However, higher PAT ratio (HR, 0.76 [95% CI, 0.61–0.94]; P =0.013), but not baseline pulse amplitude (HR, 1.15 [95% CI, 0.89–1.49]; P =0.29), was related to lower risk for incident stroke. In a sensitivity analysis by stroke subtype, higher PAT ratio was related to lower risk of incident ischemic stroke events (HR, 0.68 [95% CI, 0.53–0.86]; P =0.001). Conclusions: Novel digital PAT measures may represent a marker of stroke risk in the community.

PURPOSE: Barriers to the implementation of pharmacogenomics in clinical practice have been thoroughly discussed over the past decade. METHODS: The objective of this scoping review was to characterize the peer-reviewed literature surrounding the experiences and actions of prescribers, pharmacists, or genetic counselors when using pharmacogenomic information in real-world or hypothetical research settings. RESULTS: A total of 33 studies were included in the scoping review. The majority of studies were conducted in the US (70%), used quantitative or mixed methods (79%) with physician or pharmacist respondents (100%). The qualitative content analysis revealed five major methodological approaches: hypothetical clinical case scenarios, real-world studies evaluating prescriber response to recommendations or alerts, cross-sectional quantitative surveys, cross-sectional qualitative surveys/interviews, and a quasi-experimental real-world study. CONCLUSION: The findings of this scoping review can guide further research on the factors needed to successfully integrate pharmacogenomics into clinical care.

BACKGROUND: Glaucoma and ocular hypertension (OHT) are prevalent diseases with baseline intraocular pressure (IOP) elevations that future astronauts and spaceflight participants may suffer from. Preflight, in-flight, and postflight IOP measurements were collected aboard two U.S. Space Shuttle Program missions in normotensive control, OHT, and glaucomatous crewmembers. METHODS: Five subjects (three controls, one glaucomatous, one OHT) were studied aboard 2-wk Space Shuttle missions. Baseline IOP (triplicate; handheld tonometry) was recorded during training 12 mo preflight, in flight (114 d), and postflight (329 d). Subjective symptoms were recorded via questionnaires. Data were analyzed using a spreadsheet with two-sample t-tests. P-value < 0.05 determined significance. RESULTS: IOP increased for all in-flight vs. preflight measurements for controls (N 3, 48.9, 16.9, 5.85), OHT (N 1, 20.3), and glaucomatous (N 1, 32.2) groups. IOP eventually returned to baseline postflight [Return (R)35 d], except for the astronaut with OHT (R917). Subjective symptoms, likely multifactorial, included blurredvision, decreased visual acuity, and headaches. DISCUSSION: IOP increased during spaceflight and normalized upon return. Astronauts and commercial spaceflight participants may need screening for elevated IOP to potentially prevent sequelae related to glaucoma and OHT, the former which requires treatment in flight and the latter which may need prophylaxis. Previous studies have shown elevated IOP upon entry into microgravity with various normalization timeframes in flight and postflight. It is unclear how increased IOP relates to spaceflight-associated neuro-ocular syndrome (SANS); however, several hypotheses exist. Treatment strategies should be available for acute and chronic ocular pathology during spaceflight despite the unique challenges of eye-drop application in microgravity. Dalal SR, Ramachandran V, Khalid R, Manuel FK, Knowles JR, Jones JA. Increased intraocular pressure in glaucomatous, ocular hypertensive, and normotensive space shuttle crew. Aerosp Med Hum Perform. 2021; 92(9):728733.

Purpose To examine the benefits and feasibility of a mobile, real-time, community-based, teleophthalmology program for detecting eye diseases in the New York metro area. Design Single site, nonrandomized, cross-sectional, teleophthalmologic study. Methods Participants underwent a comprehensive evaluation in a Wi-Fi-equipped teleophthalmology mobile unit. The evaluation consisted of a basic anamnesis with a questionnaire form, brief systemic evaluations and an ophthalmologic evaluation that included visual field, intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography. The results were evaluated in real-time and follow-up calls were scheduled to complete a secondary questionnaire form. Risk factors were calculated for different types of ophthalmological referrals. Results A total of 957 participants were screened. Out of 458 (48%) participants that have been referred, 305 (32%) had glaucoma, 136 (14%) had narrow-angle, 124 (13%) had cataract, 29 had (3%) diabetic retinopathy, 9 (1%) had macular degeneration, and 97 (10%) had other eye disease findings. Significant risk factors for ophthalmological referral consisted of older age, history of high blood pressure, diabetes mellitus, Hemoglobin A1c measurement of ≥6.5, and stage 2 hypertension. As for the ocular parameters, all but central corneal thickness were found to be significant, including having an intraocular pressure >21 mm Hg, vertical cup-to-disc ratio ≥0.5, visual field abnormalities, and retinal nerve fiber layer thinning. Conclusions Mobile, real-time teleophthalmology is both workable and effective in increasing access to care and identifying the most common causes of blindness and their risk factors.

Objective To examine the relationship of visual function as assessed by visual acuity, contrast sensitivity, and multifocal electroretinography (mfERG) to macular structural and microvascular measures on optical coherence tomography (OCT) and angiography (OCTA) in individuals with diabetes. Methods This is a prospective observational study conducted at a tertiary eye care centre in India. Right eyes of 121 adults with type 2 diabetes with no diabetic retinopathy (DR), mild or moderate nonproliferative DR (NPDR) were examined. Severe NPDR, proliferative DR and diabetic macular oedema were excluded. Participants underwent assessment of glycated haemoglobin (HbA1C), blood pressure, best corrected visual acuity (LogMAR), contrast sensitivity (CS), mfERG, ultrawide field fundus photography, OCT and OCTA. Correlations were assessed by Spearman's rank correlation (rho). Results Of the total of 121 eyes, 89 had No DR, 32 had mild to moderate NPDR. In the No DR group, the LogMAR acuity was significantly and negatively correlated to central subfoveal thickness (CST) (rho = -0.420), macular vessel density (rho = -0.270) and perfusion (rho = -0.270). (ii) Contrast sensitivity correlated to foveal avascular zone circularity (rho = 0.297); (iii) mfERG P1 response densities were better with higher macular perfusion index (rho = 0.240). In the NPDR group, the LogMAR acuity also showed a significant negative correlation to CST (rho = -0.379). Other correlations were not significant. Conclusion Retinal and visual functional changes are evident in diabetic patients with No DR and are correlated to subclinical retinal structural changes detectable using multimodal imaging.

Aims While greater physical activity (PA) is associated with improved health outcomes, the direct links between distinct components of PA, their changes over time, and cardiorespiratory fitness are incompletely understood. Methods and results Maximum effort cardiopulmonary exercise testing (CPET) and objective PA measures [sedentary time (SED), steps/day, and moderate-vigorous PA (MVPA)] via accelerometers worn for 1 week concurrent with CPET and 7.8 years prior were obtained in 2070 Framingham Heart Study participants [age 54 ± 9 years, 51% women, SED 810 ± 83 min/day, steps/day 7737 ± 3520, MVPA 22.3 ± 20.3 min/day, peak oxygen uptake (VO2) 23.6 ± 6.9 mL/kg/min]. Adjusted for clinical risk factors, increases in steps/day and MVPA and reduced SED between the two assessments were associated with distinct aspects of cardiorespiratory fitness (measured by VO2) during initiation, early-moderate level, peak exercise, and recovery, with the highest effect estimates for MVPA (false discovery rate Conclusions Our findings provide a detailed assessment of relations of different types of PA with multidimensional cardiorespiratory fitness measures and suggest favourable longitudinal changes in PA (and MVPA in particular) are associated with greater objective fitness.

OBJECTIVE Despite the availability of effective medications, only a minority of asthma patients achieve guideline defined asthma control. Treatment success depends on patient concurrence to the prescribed drug and adherence to treatment. It is therefore crucial to identify the patient preferences as well as attitudes towards asthma medications. Omalizumab is recommended as a preferred option in step 5 of asthma therapy. There have been few studies to address patient perspectives on omalizumab therapy in India. METHODS This was a retrospective study. Patients with inadequate asthma control were considered for the study. Systematic evaluation was done to identify and correct modifiable factors that can worsen asthma control. Patients with persisting poor asthma control who were deemed suitable to receive this agent were evaluated with their attitudes toward acceptance or refusal and the reasons for opting out were noted. The patients who received omalizumab were followed up to determine the results of treatment and duration of adherence to therapy. RESULTS Thirty-five patients out of 51 patients chose to avoid this drug. The reasons for opting out included erroneous perception of optimal asthma control, cost of therapy, and concern about adverse effects. Patients took omalizumab for a median duration of 6 months. Improved asthma control and decreased frequency of exacerbation was noted in all patients which persisted during the 6-month follow-up. CONCLUSIONS The majority of patients needing step 5 therapy opt out of omalizumab. Cost of drug, duration of therapy and erroneous perception of good asthma control account for refusing treatment. Omalizumab affords excellent clinical benefits to patients who receive it, and the benefits extend beyond the duration of therapy.

A nurse-led cirrhosis clinic model for management of stable, compensated cirrhotic patients is practised in our unit since 2013, wherein these patients are reviewed every six months by specialist nurses in community clinics under remote supervision of hepatologists. We evaluated the experiences of patients and healthcare providers involved in the model to understand the acceptability, strengths, and limitations of the model and obtain suggestions to improve. A qualitative design using in-depth interviews was employed, followed by thematic analysis of eight patients, one attending physician both nurse and hospital clinics, four hepatologists, and three experienced specialist nurses running the nurse-led cirrhosis clinic. Patients expressed satisfaction and a good understanding of the nurse-led cirrhosis clinic, preferring it to hospital clinics for better accessibility and the unique nurse-patient relationship. Upskilling and provision of professional care in a holistic manner were appreciated by specialist nurses. The hepatologists expressed confidence and satisfaction, although they acknowledged the difference between the medical training of specialist nurses and hepatologists. The greater availability of hospital clinic time for sick patients was welcomed. Increased specialist nurse staffing, regular forums to promote specialist nurse learning, and formalization of the referral process were suggested. No adverse experiences were reported by patients or staff. The nurse-led cirrhosis clinic model for compensated liver cirrhosis was well received by patients, hepatologists, and specialist nurses. Wider implementation of the model could be considered after further investigations in other settings.

Degenerative spine disease increases in prevalence and may become debilitating as people age. Complex spine surgery may offer relief but becomes riskier with age. Efforts to lessen the physiological impact of surgery through minimally invasive techniques and enhanced recovery programs mitigate risk only after the decision for surgery. Frailty assessments outperform traditional tools of perioperative risk stratification. The extent of frailty predicts complications after spine surgery such as reoperation for infection and 30-day mortality, as well as elements of social cost such as hospital length of stay and discharge to an advanced care facility. Symptoms of spine disease overlap with phenotypic markers of frailty; therefore, different frailty assessment tools may perform differently in patients with degenerative spine disease. Beyond frailty, however, cognitive decline and psychosocial isolation may interact with frailty and affect achievable surgical outcomes. Prehabilitation, which has reduced perioperative risk in colorectal and cardiac surgery, may benefit potential complex spine surgery patients. Typical prehabilitation includes physical exercise, nutrition supplementation, and behavioral measures that may offer symptomatic relief even in the absence of surgery. Nonetheless, the data on the efficacy of prehabilitation for spine surgery remains sparse and barriers to prehabilitation are poorly defined. This narrative review concludes that a frailty assessment-potentially supplemented by an assessment of cognition and psychosocial resources-should be part of shared decision-making for patients considering complex spine surgery. Such an assessment may suffice to prompt interventions that form a prehabilitation program. Formal prehabilitation programs will require further study to better define their place in complex spine care.

Background Worldwide around 2 million deaths occur every year due to diarrhoeal illnesses among children less than 5 years of age. Among diarrhoeagenic Escherichia coli, Enteropathogenic E. coli (EPEC) is highly prevalent in both community and hospital settings and is one of the main causes of persistent diarrhea in children in developing countries. EPEC remains underdiagnosed in India due to lack of conventional tool for identification. Materials and methods We in this study investigated the prevalence and regional variation of EPEC in paediatric population suffering from diarrhoea in East Delhi, India. Two hundred stool samples were collected from children, aged between 0.5 and 5 years, with acute diarrhoea. E. coli were identified by conventional tests and PCR. Results We observed 7% atypical EPEC (aEPEC) and 2.5% typical EPEC (tEPEC), with an overall 9.5% EPEC prevalence amongst total samples. E. coli phylogenetic group A was the predominant. The most common age group affected was 6–23 months with common symptoms being vomiting, watery diarrhoea and severe dehydration. High drug resistance pattern was observed in EPEC isolates. Conclusion The study depicts a changing trend of aEPEC over tEPEC in children less than 5 years with diarrhoea, an emerging drug resistant enteropathogen and a public health concern demanding monitoring and surveillance.

The purpose of this study is to determine the usefulness of computed tomography in demonstrating numerous benign and malignant lesions that may affect the trachea primarily or secondarily. The characteristics of imaging features and the extent of spread of these unusual lesions can be recognized on cross-sectional imaging. In this article, we describe the typical imaging appearance of the various tracheal lesions and discuss the role of Multidetector Computed tomography in enhancing the diagnostic value of the various tracheal lesions in clinical practice.

Introduction Association between arterial vascular dysfunction and risk of venous thromboembolism (VTE) is uncertain. We determined the associations between comprehensive measures of arterial vascular function and risk of incident VTE in a community-based cohort study with robust longitudinal follow-up. Materials and methods In the Framingham Heart Study Original, Offspring, Third Generation, and Omni cohorts, we measured carotid-femoral pulse wave velocity and central pulse pressure (n = 8261, age 51.5 ± 15.5 years, 54% women), flow-mediated dilation and hyperemic velocity (n = 6540, age 47.9 ± 14.1 years, 54% women), and peripheral arterial tonometry ratio (n = 4998, age 54.3 ± 16.0 years, 52% women). Deep venous thrombosis and pulmonary embolism were diagnosed with imaging studies and adjudicated by three Framingham Heart Study physicians. Results and conclusions The rate of incident VTE was 1.6–2.1 per 1000 person-years during mean follow-up of 8.5–11.2 years. In age- and sex-adjusted Cox proportional hazards regression models, carotid-femoral pulse wave velocity was associated with increased risk of VTE (HR 1.32, 95% CI 1.05–1.66, p = 0.02), however the association was no longer statistically significant after multivariable adjustment (HR 1.24, 95% CI 0.96–1.61, p = 0.10). None of the other vascular variables were associated with the risk of VTE in any of the models. In our comprehensive examination of arterial vascular function and risk of VTE, we did not observe any association between select arterial function measures and risk of VTE after multivariable adjustment.

Objective To determine the threshold of the inotropic score (IS) and vasoactive–inotropic score (VIS) for predicting mortality in pediatric septic shock. Method This retrospective cohort study included children aged 1 mo to 13 y with septic shock, requiring vasoactive medication. The area under curve receiver operating characteristic (AUROC) was calculated using mean IS and mean VIS to predict PICU mortality, and Youden index cut points were generated. Sensitivity, specificity, and binary regression analysis were performed. Results A total of 176 patients were enrolled (survivor, n = 72, 41% and nonsurvivor, n = 104, 59%). For predicting the PICU mortality, AUROC (95% CI) of IS was 0.80 (0.74–0.86) [sensitivity of 88.5 (80.7–94) and specificity of 58.3 (46.1–69.8)] and AUROC of VIS was 0.88 (0.82–0.92) [sensitivity of 83.7 (75.1–90.2) and specificity of 80.6 (69.5–89)]. The respective cutoff scores of IS and VIS were 28 and 42.5. On regression analysis (adjusted odds ratio, 95% CI), illness severity (PRISM-III) (1.12, 1.05–1.12), worst lactate value (1.31, 1.08–1.58), IS (> 28) (3.98, 1.24–12.80), and VIS (> 42.5) (4.66, 1.57–13.87) independently predicted the PICU mortality (r2 = 0.625). Conclusion Threshold of inotropic score (> 28) and vasoactive–inotropic score (> 42.5) were independently associated with PICU mortality. In addition to IS and VIS, severity and worst lactate value independently predicted septic shock mortality in PICU.

Objective: Goodpasture's syndrome (GPS) is the association of pulmonary haemorrhage with acute kidney injury (AKI) resulting from injury by auto-antibodies. Its de novo occurrence in pregnancy is extremely rare with only few cases reported. High risk of mortality and lack of consensus in treatment warrants its reporting. Case report: A 24 year old primigravida, with no history suggestive of renal disease, presented to us in her third trimester with anuria. She was initially managed as sepsis or preeclampsia related AKI. However, even after delivery there was no improvement in kidney function with hemodialysis and she developed hemoptysis. Renal biopsy made a diagnosis of Anti-Glomerular Basement Membrane disease. With careful multi-disciplinary treatment, she delivered a live born baby and was discharged under stable condition on hemodialysis, currently awaiting a kidney transplant. Conclusion: This case highlights that the current management for GPS should be revised to improve the outcome of AKI. Also, it determines how important it is for obstetricians to consider whether a pregnancy should be terminated to improve the outcome of AKI in pregnant patients with GPS