Non-simultaneous kidney exchange cycles in resource-restricted countries without non-directed donation - a prospective single-center cohort study.

Recent reports suggest that bridge-donor reneging is rare (1.5%) in non-simultaneous kidney exchange chains. However, in developing countries, the non-directed donors who would be needed to initiate chains are unavailable, and furthermore, limited surgical space and resources restrain the feasibility of simultaneous kidney exchange cycles. Therefore, the aim of this study was to evaluate the bridge-donor reneging rate during non-simultaneous kidney exchange cycles (NSKEC) in a prospective single-center cohort study (n = 67). We describe the protocol used to prepare co-registered donor-recipient pairs for non-simultaneous surgeries, in an effort to minimize the reneging rate. In addition, in order to protect any recipients who might be left vulnerable by this arrangement, we proposed the use of standard criteria deceased-donor kidneys to rectify the injustice in the event of any bridge-donor reneging. We report 17 successful NSKEC resulting in 67 living-donor kidney transplants (LDKT) using 23 bridge-donors without donor renege and no intervening pairs became unavailable. We propose that NSKEC could increase LDKT, especially for difficult-to-match sensitized pairs (25 of our 67 pairs) in countries with limited transplantation resources. Our study confirms that NSKEC can be safely performed with careful patient-donor selection and non-anonymous kidney exchanges.

Two Decades of Deceased Donor Kidney Transplantation at Ahmedabad, India.

OBJECTIVES: Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. MATERIALS AND METHODS: This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. RESULTS: Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. CONCLUSIONS: Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

Author Correction: Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.

The original version of this Article omitted a declaration from the competing interests statement, which should have included the following: 'K.P.W. is President of Tempus Lab, Inc., Chicago, IL, USA'. This has now been corrected in both the PDF and HTML versions of the Article.

Author Correction: Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc., Chicago, IL, USA was inadvertently omitted.This has now been corrected in both the PDF and HTML versions of the Article.

Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.

Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis.

Anesthetic management of two cases of Bardet-Biedl syndrome for renal transplantation.

Bardet-Biedl syndrome (BBS) is a multisystem autosomal recessive disorder with clinical and genetic heterogeneity. It is a type of ciliopathy characterized by retinal dystrophy, central obesity, polydactyly, cognitive impairment, and gonadal and renal dysgenesis. It has been suggested that the involved proteins attach to the basal body of ciliated cells making this a disorder of ciliary dysfunction. We report two cases of typical BBS in a 17-year-old female and 29-year-old male patient, who presented for live-related renal transplant. We discuss the relevant points of the syndrome regarding anesthetic management.

Anesthetic management of Morgagni hernia repair in an elderly woman.

Adult onset congenital diaphragmatic hernia (CDH) is uncommon but not rare. Morgagni hernia is a rare variant of CDH. The defect tends to be small and patients may remain asymptomatic and diagnosed incidentally. When these patients become symptomatic, they usually present with gastrointestinal and cardiorespiratory symptoms or sometimes as an emergency due to obstruction or strangulation of herniated viscera. Chest radiograph, computed tomography scan, and magnetic resonance imaging are the imaging modalities used for diagnosis of CDH. Cardiopulmonary compromise due to mass effect of hernial contents on lungs, heart and great vessels, and obstruction or strangulation of herniated viscera poses the special challenge before anesthesiologists. Our patient was diagnosed to have Morgagni hernia, at the age of 72 years and underwent laparotomy for the same. This case highlights the key feature of the successful anesthetic management of adult onset CDH.

The effects of dexmedetomidine on attenuation of hemodynamic changes and there effects as adjuvant in anesthesia during laparoscopic surgeries.

BACKGROUND: As an anesthetic adjuvant dexmedetomidine has been shown to provide good perioperative hemodynamic stability with minimum alveolar concentration sparing effect on inhalational anesthetic agents during laparoscopic surgeries performed under general anesthesia. AIM: The study was planned to investigate the effects of dexmedetomidine on attenuation of hemodynamic changes and requirements of intra-operative analgesic and inhalational anesthetic during laparoscopic surgeries and its postoperative side effects. MATERIALS AND METHODS: A total of 70 patients scheduled for elective laparoscopic surgeries were randomized to receive bolus infusion of dexmedetomidine (group D) or saline (group S) 1 mcg/kg/h, followed by continuous infusion of the same, at the rate of 0.5 mcg/kg/h. Anesthesia was maintained with nitrous oxide in oxygen, muscle relaxant and isoflurane. Supplementation with end-tidal isoflurane was considered when heart rate (HR) and mean arterial blood pressure (BP) exceeded 20% of the baseline value. Hemodynamics, end-tidal isoflurane concentration and adverse events were recorded. RESULTS: Intra-operative mean HR and mean BP in group D were lower than group S (P < 0.05) throughout the laparoscopy surgery. Requirement of intra-operative fentanyl, end-tidal isoflurane and postoperative tramadol were significantly more in group S compared to group D (P < 0.05) Statistically significant nausea and vomiting were noted in group S. Undue sedation and other adverse effects are comparable in both the groups. CONCLUSION: Dexmedetomidine as an adjuvant in general anesthesia for laparoscopic surgeries provided a stable hemodynamic profile in the perioperative period and effectively blunted pressor response to intubation and extubation, leading to minimal requirements for additional analgesics and potent inhalational agents. There were less adverse events.

Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2.

BACKGROUND: Hereditary Spastic Paraplegia (HSP) represents a large group of clinically and genetically heterogeneous disorders linked to over 70 different loci and more than 60 recognized disease-causing genes. A heightened vulnerability to disruption of various cellular processes inherent to the unique function and morphology of corticospinal neurons may account, at least in part, for the genetic heterogeneity. METHODS: Whole exome sequencing was utilized to identify candidate genetic variants in a four-generation Siberian kindred that includes nine individuals showing clinical features of HSP. Segregation of candidate variants within the family yielded a disease-associated mutation. Functional as well as in-silico structural analyses confirmed the selected candidate variant to be causative. RESULTS: Nine known patients had young-adult onset of bilateral slowly progressive lower-limb spasticity, weakness and hyperreflexia progressing over two-to-three decades to wheel-chair dependency. In the advanced stage of the disease, some patients also had distal wasting of lower leg muscles, pes cavus, mildly decreased vibratory sense in the ankles, and urinary urgency along with electrophysiological evidence of a mild distal motor/sensory axonopathy. Molecular analyses uncovered a missense c.2155C > T, p.R719W mutation in the highly conserved GTP-effector domain of dynamin 2. The mutant DNM2 co-segregated with HSP and affected endocytosis when expressed in HeLa cells. In-silico modeling indicated that this HSP-associated dynamin 2 mutation is located in a highly conserved bundle-signaling element of the protein while dynamin 2 mutations associated with other disorders are located in the stalk and PH domains; p.R719W potentially disrupts dynamin 2 assembly. CONCLUSION: This is the first report linking a mutation in dynamin 2 to a HSP phenotype. Dynamin 2 mutations have previously been associated with other phenotypes including two forms of Charcot-Marie-Tooth neuropathy and centronuclear myopathy. These strikingly different pathogenic effects may depend on structural relationships the mutations disrupt. Awareness of this distinct association between HSP and c.2155C > T, p.R719W mutation will facilitate ascertainment of additional DNM2 HSP families and will direct future research toward better understanding of cell biological processes involved in these partly overlapping clinical syndromes.

BILATERAL ADDUCTOR VOCAL CORD PALSY: COMPLICATION OF PROLONGED INTRAOPERATIVE HYPOTENSION AFTER ENDOTRACHEAL INTUBATION.

Endotracheal intubation for general anesthesia is usually a safe procedure. However, postoperative sore throat and mild hoarseness may occur due to laryngeal edema but bilateral vocal cord paralysis as a result of recurrent laryngeal nerve injury is a rare complication. We report a case of bilateral adductor vocal cord palsy following general anesthesia for abdominal surgery. Clinical presentation was hoarseness, aspiration pneumonia and hypoxemia requiring ventilatory support. Neuropraxia of recurrent laryngeal nerve due to prolong intra-operative hypotension, even with normal endotracheal tube cuff pressure was the likely mechanism.

Bradycardia and severe vasospasm caused by intramyometrial injection of vasopressin during myomectomy.

Vasopressin is often used locally to reduce blood loss during surgery. Vasopressin has longest clinical effect, but its systemic effects may be profound and pose significant challenges for the anesthesiologist and it can also sometimes cause lethal complications. The loss of peripheral pulse along with bradycardia, non-measurable arterial blood pressure, and cardiac complications have been reported after myometrial injection of vasopressin. Here, we describe a patient with multiple uterine myomas who developed severe bradycardia, non-measurable blood pressure by non-invasive means and loss of peripheral pulse after myometrial injection of vasopressin at a total dose of 20 units (1 unit/ml) with documentation of severe peripheral arterial vasospasm and increased proximal blood pressure. The patient was successfully resuscitated.

Anaesthetic management of a case of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a rare headache syndrome characterized by prolonged elevation of intracranial pressure without related pathology in either the brain or the composition of cerebrospinal fluid. Herein, we provide a brief review of the clinical presentation of IIH and the anaesthetic considerations in a female posted for transcervical resection of the endometrium and right nephrectomy with the disorder. Most of patients with IIH are reported during pregnancy and came for management of labour and delivery. To our knowledge no such case has been described previously.

Randomized double blind trial of intraperitoneal instillation of bupivacaine and morphine for pain relief after laparoscopic gynecological surgeries.

BACKGROUND: Intraperitoneal injection of anesthetic has been proposed to minimize postoperative pain after laparoscopic surgery. So a randomized, placebo-controlled study was conducted to compare the effectiveness of intraperitoneal bupivacaine with or without morphine for postoperative analgesia after laparoscopic gynecological surgeries. METHODS: A total of 90 ASA I and II female patients scheduled for laparoscopic gynecological procedures were enrolled in the randomized double blind prospective study. The drug was injected intraperitoneally before the removal of trocar at the end of surgery. In group BM (n=30): 0.25% bupivacaine 30 ml + 2 mg morphine, in group BO (n=30) 30 ml 0.25% bupivacaine and in group C (n=30) 30 ml of saline was injected intraperitoneally. Postoperative quality of analgesia was assessed by VAS (0-100), for 24 hours and when VAS >40, rescue analgesic was administered. Total dose of rescue analgesia and side effects were noted. RESULTS: INTRAPERITONEAL INSTILLATION OF BUPIVACAINE AND MORPHINE SIGNIFICANTLY REDUCES IMMEDIATE POSTOPERATIVE PAIN (VAS: 23.33±6.04 vs. 45.5±8.57). It also reduces pain at 4 hours after surgery in the BM group (VAS 24±12.13 vs. 41.17±7.27 in the BO group). The time of administration of first rescue analgesic was significantly higher in the BM group (6.15 hours) compared to the BO group (4.51 hours). The total dosage of rescue analgesic was more in the BO and C groups compared to the BM group. CONCLUSION: Addition of morphine to local anesthetic significantly prolonged the time to first rescue analgesic requirement and the total consumption of rescue analgesic in 24 hours without any significant increase in adverse events.

Postoperative analgesia with epidural opioids after cesarean section: Comparison of sufentanil, morphine and sufentanil-morphine combination.

BACKGROUND: Epidural analgesia with opioid provides good control of postoperative pain in cesarean section, thereby improving the mother's ability to mobilize and interact with her newborn infant. AIM: The aim of this study is to evaluate and compare the analgesic actions and side effects of epidural analgesia with sufentanil, morphine or combination of the two after cesarean section. MATERIALS AND METHODS: 60 women undergoing elective cesarean section were allocated into three groups of 20 each in a randomized blinded fashion. Epidural analgesia was administered with sufentanil 50 mcg in Group S; morphine 4 mg in Group M; and, a combination of sufentanil 25 mcg and morphine 2 mg was used in Group SM. Analgesic efficacy in terms of onset of action and duration of analgesia was assessed by using the Visual Analog Scale (0 to 10 cm) for 24 hours. Number of opioid doses needed in 24 hours was noted. Side effects like respiratory depression /excessive sedation, pruritus and nausea were recorded. RESULTS: Onset of action were at 7.6 ± 1.5 minutes in group S, 67.6 ± 1.5 minutes in group M and 12.2 ± 2.6 minutes in group SM. Duration of analgesia was longer in group M 17.5 ± 1.9 hours and SM 13.8 ± 1.6 hours than in group S 5.2 ± 1.2 hours. More doses of analgesia were required in group S compared to group M and SM. Side effects were comparable in the three groups. CONCLUSION: Epidural administration of a combination of sufentanil and morphine offered the advantage of faster onset of action and longer duration of analgesia as compared to the two drugs administered alone.

Medication error: Subarachnoid injection of tranexamic acid.

Some factors have been identified as contributing to medical errors, such as labels, appearance and location of ampoules. We present a case of accidental injection of tranexamic acid instead of Bupivacaine during spinal anaesthesia. One minute after the injection of 3 mL of the solution, the patient developed myoclonus of her lower extremities. Accidental intrathecal injection of the wrong drug was suspected and a used ampoule of tranexamic acid was discovered in the trash can. The ampoules of Bupivacaine (5 mg/mL, trade name "Sensovac Heavy") and tranexamic acid (500 mg/mL, Trade name "Nexamin") were similar in appearance. Her myoclonus was successfully treated with phenytoin, sodium valproate, thiopental sodium infusion, midazolam infusion and supportive care of haemodynamic and respiratory systems. The surgery was temporarily deferred. The patient's condition progressively improved to full recovery.

Trimester of maternal gestational weight gain and offspring body weight at birth and age five.

To investigate associations of trimester-specific GWG with fetal birth size and BMI at age 5 years. We examined 3,015 singleton births to women without pregnancy complications from the Child Health and Development Studies prospective cohort with measured weights during pregnancy. We used multivariable regression to examine the associations between total and trimester gestational weight gain (GWG) and birth weight for gestational age and child BMI outcomes, adjusting for maternal age, race/ethnicity, education, marital status, parity, pre-pregnancy body mass index (BMI), and smoking; paternal overweight, gestational age, and infant sex. We explored differences in associations by maternal BMI and infant sex. GWG in all trimesters was significantly and independently associated with birth weight with associations stronger, though not significantly, in the second trimester. First trimester GWG was associated with child BMI outcomes (OR for child overweight = 1.05; 95% CI = 1.02, 1.09). Each kg of first trimester GWG was significantly associated with increased child BMI z-score in women of low (ß = 0.099; 95% CI = 0.034, 0.163) and normal (ß = 0.028; 95% CI = 0.012, 0.044), but not high pre-pregnancy BMI. GWG in all trimesters was associated with birth weight; only first trimester GWG was associated with child BMI. If replicated, this information could help specify recommendations for maternal GWG and elucidate mechanisms connecting GWG to child BMI.