End-recovery QTc: a useful metric for assessing genetic variants of unknown significance in long-QT syndrome

QTc for Assessing Significance of LQT Variants. Introduction: Genetic variants represent benign single‐nucleotide polymorphisms, disease causing mutations or variants of unknown significance (VUS). Resting, exercise, and recovery QTc intervals have been utilized to detect long‐QT syndrome (LQTS) mutations. We sought to provide clinical data that may assist in classifying the presented VUS as disease causing/benign and to determine whether resting and/or end‐recovery QT parameters can evaluate the significance of VUS. Methods and Results: Twenty‐six patients with a VUS in genes associated with LQTS (15 females, age 38 ± 16 years) and 26 age and gender matched controls (age 37 ± 20 years) were included. There were 10 VUS (5 KCNQ1, 4 KCNH2, 1 KCNE1) in 12 families. All but 1 VUS was associated with sudden cardiac death (SCD), aborted SCD or Torsade de pointes. A Schwartz score of ≥3.5 was observed in at least 1 family member with each VUS. Resting QTc was marginally longer in VUS patients compared with controls (458 ± 48 vs 437 ± 25, P = 0.052). A prolonged resting QTc (>470 ms males, >480 ms females) identified 6 VUS carriers and 1 control. VUS carriers had a substantially longer end‐recovery QTc (502 ± 68 vs 427 ± 17, P < 0.01) with an end‐recovery QTc > 445 ms in 20/26 VUS patients compared to 2/26 controls (P < 0.01). The area under the receiver operating characteristic curve for resting QTc was 0.68 (95% CI, 0.53–0.83, P = 0.03) compared to the end‐recovery QTc of 0.88 (95% CI, 0.76–0.99, P < 0.0001). Conclusion: Variants in the current study appear to be disease causing. The end‐recovery QTc is a useful metric when interpreting LQT VUS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 637–642, June 2012)     

Corticosteroid Therapy, Vitamin D Status, and Inflammatory Cytokine Profile in the HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Background.?Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in patients coinfected with human immunodeficiency virus (HIV) and tuberculosis starting antiretroviral therapy (ART) is associated with hypercytokinemia. As adjunctive corticosteroid therapy and vitamin D have immunomodulatory properties, we investigated the relationship between cytokine/chemokine profiles, corticosteroid use, and vitamin D deficiency in TB-IRIS patients. Methods.?Plasma from 39 TB-IRIS and 42 non-IRIS patients was collected during a prospective study of HIV-associated tuberculosis patients starting ART. In total, 26% of patients received corticosteroid (CTC) therapy pre-ART for severe tuberculosis. Concentrations of total 25-hydroxyvitamin D (25(OH)D) and 14 cytokines/chemokines were determined at ART initiation and 2 weeks later. Results.?Patients prescribed concurrent CTC had lower interferon γ (IFN-γ), IP-10, tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-10, IL-12p40, and IL-18 pre-ART (P?≤?.02). TB-IRIS presented at 12 days (median) of ART, irrespective of CTC use. In patients who developed TB-IRIS (not on CTC) IL-6, IL-8, IL-12p40, IL-18, IP-10, and TNF increased during 2 weeks (P?≤?.04) of ART. Vitamin D deficiency (total 25(OH)D <75?nmol/L) was highly prevalent (89%) at baseline. Although vitamin D deficiency at either baseline or 2 weeks was not associated with TB-IRIS, in those not on CTC the median 25(OH)D decreased during 2 weeks (P?=?.004) of ART. Severe vitamin D deficiency (total 25(OH)D <25?nmol/L) was associated with higher baseline TNF, IL-6, and IL-8 irrespective of IRIS status. Conclusions.?CTC modifies the inflammatory profile of those who develop TB-IRIS. The association between severe vitamin D deficiency and elevated proinflammatory cytokines support a study of vitamin D supplementation in HIV-TB co-infected patients starting ART.     

Vasoocclusion by sickled RBCs in 5 autopsy cases of sudden death

Mortality in sickle cell disease is high at young age group. So it is necessary to find out the cause of death in young patients with sickle cell disease. We are presenting 5 cases of sudden death in young adults with undiagnosed sickle cell disease. The provocative factors for those terminal events were vasoocclusive crisis. In our patients crisis was secondary to fever (infection), conductive arrhythmia, cardiovascular collapse, post partum shock and hemorrhage. On microscopic examination of viscera, not a single patient showed signs of chronic organ damage, sequestration crisis or acute chest syndrome, which are the common causes of death in sickle cell disease.     

In-house growth-promoting transport system for Neisseria gonorrhoeae

Eno powder (GlaxoSmithKline), an antacid preparation readily available over the counter, was used instead of a CO(2) generator for the growth of 15 strains of Neisseria gonorrhoeae obtained from men with urethritis. Due to its easy accessibility and low cost, Eno powder can be useful in developing countries for transporting clinical specimens from resource-poor peripheral labs to reference laboratories.     

An analysis of qualitative and mixed methods abstracts from Japanese,UK and US primary care conferences

Background

As research in family medicine covers varied topics, multiple methodologies such as qualitative research (QR) and mixed methods research (MMR) are crucial. However, we do not know about the difference in the proportion of QR or MMR between Japan, the UK and the US. This knowledge is needed to shape future research within countries with developing primary care such as Japan and other Asian countries. This study aims to describe the use of QR and MMR in Japanese primary care and compare this to the UK and US; then to make informed recommendations for primary care research.

Methods

A repeated cross-sectional study (2012–2016) based on the abstracts submitted to the annual conferences of the Japanese Primary Care Association in Japan, the Royal College of General Practitioners in the UK, and the North American Primary Care Research Group in the US and other North American countries. The proportions of QR/MMR among all the posters and paper presentations for each of these three conferences were assessed. Also examined were trends and types of qualitative techniques for all three countries and participants/settings for Japan.

Results

There were 1080 abstracts for Japan, 575 for UK and 3614 for US conferences. QR/MMR proportions were 7.5%, 15.1% and 28.1%, respectively. Japan’s proportion was lower than that of UK and US (p?<?0.001). The proportion was increasing over time for the UK (p?=?0.02). Steps for coding and analyses was most popular for Japan, thematic analysis for the UK and grounded theory for the US. Primary care doctors and hospitals were the commonest contexts for Japan.

Conclusions

QR and MMR were not as popular in primary care in Japan compared to the UK and the US, whereas their use was increasing in the UK. Approaches, participants and settings may differ among these countries. Education and promotion of QR/MMR and multi-disciplinary collaborations need to be recommended in Japan with developing primary care.

     

Nephron injury induced by diagnostic ultrasound imaging at high mechanical index with gas body contrast agent

The right kidney of anesthetized rats was imaged with intermittent diagnostic ultrasound (1.5 MHz; 1-s trigger interval) under exposure conditions simulating those encountered in human perfusion imaging. The rats were infused intravenously with 10 microL/kg/min Definity (Bristol-Myers Squibb Medical Imaging, Inc., N. Billerica, MA, USA) while being exposed to mechanical index (MI) values of up to 1.5 for 1 min. Suprathreshold MI values ruptured glomerular capillaries, resulting in blood filling Bowman's space and proximal convoluted tubules of many nephrons. The re-establishment of a pressure gradient after hemostasis caused the uninjured portions of the glomerular capillaries to resume the production of urinary filtrate, which washed some or all of the erythrocytes out of Bowman's space and cleared blood cells from some nephrons into urine within six hours. However, many of the injured nephrons remained plugged with tightly packed red cell casts 24 h after imaging and also showed degeneration of tubular epithelium, indicative of acute tubular necrosis. The additional damage caused by the extravasated blood amplified that caused by the original cavitating gas body. Human nephrons are virtually identical to those of the rat and so it is probable that similar glomerular capillary rupture followed by transient blockage and/or epithelial degeneration will occur after clinical exposures using similar high MI intermittent imaging with gas body contrast agents. The detection of blood in postimaging urine samples using standard hematuria tests would confirm whether or not clinical protocols need to be developed to avoid this potential for iatrogenic injury.     

Futility and the Care of Surgical Patients: Ethical Dilemmas

Futility has been a contentious topic in medicine for several decades. Surgery in critical or end-of-life situations often raises difficult questions about futility. In this article, we discuss the definition of futility, methods for resolving futility disputes, and some ways to reframe the futility debate to a more fruitful discussion about the goals of care, better communication between surgeon and patient/surrogate, and palliative surgical care. Many definitions of futile therapy have been discussed. The most controversial of these is “qualitative futility” which describes a situation in which the treatment provided is likely to result in an unacceptable quality of life. This is an area of continued controversy because it has been impossible to identify universally held beliefs about acceptable quality of life. Many authors have described methods for resolving futility disputes, including community standards and legalistic multi-step due process protocols. Others, however, have abandoned the concept of futility altogether as an unhelpful term. Reframing the issue of futility as one of inadequate physician–patient communication, these authors have advocated for methods of improving communication and strengthening the patient–physician relationship. Finally, we discuss the utilization of consultants who may be of use in resolving futility disputes: ethics committees, palliative care specialists, pastoral care teams, and dedicated patient advocates. Involving these specialists in a futility conflict can help improve communication and provide invaluable assistance in arriving at the appropriate treatment decision.     

Robotic Kidney Transplantation with Regional Hypothermia: A Step-by-step Description of the Vattikuti Urology Institute–Medanta Technique (IDEAL Phase 2a)

Background

We recently reported on preclinical and feasibility studies (Innovation, Development, Exploration, Assessment, Long-term study [IDEAL] phase 0–1) of the development of robotic kidney transplantation (RKT) with regional hypothermia. This paper presents the IDEAL phase 2a studies of technique development.

Objectives

To describe the technique of RKT with regional hypothermia developed at two tertiary care institutions (Vattikuti Urology Institute and Medanta Hospital). We report on the safety profile and early graft function in these patients.

Design, setting, and participants

This is a prospective study of 50 consecutive patients who underwent live-donor RKT at Medanta Hospital following a 3-yr planning/simulation phase at the Vattikuti Urology Institute. Demographic details, and perioperative and postoperative outcomes are reported for the initial 25 recipients who have completed a minimum 6-mo follow-up.

Surgical procedure

Positioning and port placement were similar to that used for robotic radical prostatectomy. Allograft cooling was achieved by ice slush delivered through a GelPOINT device. The accompanying video details the operative technique.

Outcome measurements and statistical analysis

The primary outcome was posttransplant graft function. Secondary outcomes included technical success or failure and complication rates.

Results and limitations

Fifty patients underwent RKT successfully, 7 in the phase 1 and 43 in the phase 2 stages of the study. For the initial 25 patients, mean console, warm ischemia, arterial, and venous anastomotic times were 135, 2.4, 12, and 13.4 min, respectively. All grafts were cooled to 18–20°C with no change in core body temperature. All grafts functioned immediately posttransplant and the mean serum creatinine level at discharge was 1.3 mg/dl (range: 0.8–3.1 mg/dl). No patient developed anastomotic leaks, wound complications, or wound infections. At 6-mo of follow-up, no patient had developed a lymphocele detected on CT scanning. Two patients underwent re-exploration, and one patient died of congestive heart failure (1.5 mo posttransplant).

Conclusions

RKT with regional hypothermia is safe and reproducible when performed by a team skilled in robotic surgery.

Patient summary

RKT is safe and effective when performed by surgeons experienced in robotic techniques.     

Multiaxial high-modularity spinopelvis (HMSP) fixation device in neuromuscular scoliosis: a comparative study

Purpose

To compare radiological and clinical results in patients operated for neuromuscular scoliosis with pelvic fixation using high-modularity spinopelvic screw (HMSP) designed by authors.

Methods

Of 54 patients with neuromuscular scoliosis, group 1 comprised of 27 patients with conventional pelvic fixation; and group 2 comprised of 27 patients using HMSP. Results were evaluated radiologically and functionally. We compared preoperative and postoperative complications, especially the loosening or breakage of spinopelvis fixation device, failure of fixation, and the change of shadow around the spinopelvis fixation device.

Results

There was no difference of correctional power, preoperative average Cobb’s angle of each group was 79.8 and 75 to postoperative 30.2 and 28.3 (P < 0.05). Pelvic obliquity improved from average 18.3°–8.9° in group I and average 24.3°–12.5° in group II (P < 0.05). However, there was no difference between two groups (P > 0.05). Average blood loss was 2,698 ml in group 1 and 2,414.8 ml in group 2 (P > 0.05). Average operative time was 360 min in group 1 and 332 min in group 2 (P = 0.30). There was no difference found between two groups regarding gait and functional evaluation. On the all cases of group 1 and 2, the change of shadow around the spinopelvis fixation device was observed. There was one case of the fracture of spinopelvis fixation device in group I.

Conclusion

There was no difference of Cobb’s angle and correctional power between the groups using HMSP when compared with the group using standard spinopelvis fixation device. Therefore, HMSP can be used more effectively in case of neuromuscular scoliosis.     

Does delaying surgery in immature adolescent idiopathic scoliosis patients with progressive curve,lead to addition of fusion levels?

Purpose

To analyze the changes in the curve extent, pattern and the fusion level in adolescent idiopathic scoliosis (AIS) patients who undergo delayed surgery instead of early surgery.

Methods

Thirty-five immature AIS patients whose radiographs demonstrated an initial primary curve of more than 40° with a subsequent increase of 10° before attaining skeletal maturity with brace were enrolled. The initial and the final radiographs taken before surgery were compared to assess the changes in curve extent, pattern and the fusion levels as recommended by King’s, Lenke’s and Suk’s guidelines.

Results

The average age of 35 AIS patients was 12.7 ± 1.6 years. The time interval between initial and final radiography was 39.3 ± 20.2 months and the degree of progress of the primary curve was 13 ± 9.7°. Fusion levels changed in 33 (94.2 %), 33 (94.2 %) and 32 (91.4 %) patients according to King’s, Lenke’s and Suk’s guidelines, respectively. Curve pattern was changed in 2 (5.7 %), 12 (34.3 %) and 10 (28.6) patients by King’s, Lenke’s and Suk’s guidelines. The mean number of levels requiring fusion increased from 9.4 ± 2.1 at initial visit to 11.1 ± 1.8 at the final follow-up using King’s guidelines, 9.7 ± 2.2–11.6 ± 2.0 as per Lenke’s guidelines and 9.1 ± 2.0–11.5 ± 2.3 when fusion was planned using Suk’s guidelines (p < 0.001 in all guidelines).

Conclusions

Delay of surgery in immature AIS patients whose Cobb’s angle exceed 40° initially and showing subsequent progression of the curve, of more than 10° can lead to alterations in the curve pattern and the need for increase in fusion levels.