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.

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.

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.

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.

Epidemiology of Viliuisk encephalomyelitis in Eastern Siberia.

BACKGROUND: Viliuisk encephalomyelitis is a disorder that starts, in most cases, as an acute meningoencephalitis. Survivors of the acute phase develop a slowly progressing neurologic syndrome characterized by dementia, dysarthria, and spasticity. An epidemic of this disease has been spreading throughout the Yakut Republic of the Russian Federation. Although clinical, neuropathologic, and epidemiologic data suggest infectious etiology, multiple attempts at pathogen isolation have been unsuccessful. METHODS: Detailed clinical, pathologic, laboratory, and epidemiologic studies have identified 414 patients with definite Viliuisk encephalomyelitis in 15 of 33 administrative regions of the Yakut Republic between 1940 and 1999. All data are documented in a Registry. RESULTS: The average annual Viliuisk encephalomyelitis incidence rate at the height of the epidemic reached 8.8 per 100,000 population and affected predominantly young adults. The initial outbreak occurred in a remote isolated area of the middle reaches of Viliui River; the disease spread to adjacent areas and further in the direction of more densely populated regions. The results suggest that intensified human migration from endemic villages led to the emergence of this disease in new communities. Recent social and demographic changes have presumably contributed to a subsequent decline in disease incidence. CONCLUSIONS: Based on the largest known set of diagnostically verified Viliuisk encephalomyelitis cases, we demonstrate how a previously little-known disease that was endemic in a small indigenous population subsequently reached densely populated areas and produced an epidemic involving hundreds of persons.

Encoding a superantigen by Staphylococcus aureus does not affect clinical characteristics of infected atopic dermatitis lesions.

BACKGROUND: Bacterial infection with Staphylococcus aureus is a known trigger for the worsening of atopic dermatitis (AD). Staphylococcal superantigens have been theorized to make a potential contribution to this worsening of AD seen with infection. OBJECTIVES: We sought to assess whether encoding a superantigen by S. aureus affects the inflammatory characteristics of impetiginized AD skin lesions. METHODS: Fifty-two children with clinically impetiginized lesions of AD which were positive for S. aureus were enrolled in this study. A lesion was graded clinically using the Eczema Area and Severity Index (EASI), and then wash fluid was obtained from the lesion for quantitative bacterial culture, and measurement of bacterial products lipoteichoic acid and staphylococcal protein A and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities and the presence of a superantigen. RESULTS: Fifty-four per cent (28 of 52) of the staphylococcal isolates encoded a superantigen. The presence of a superantigen had no significant effect on EASI score, amounts of bacterial products or inflammatory cytokines in the AD lesion. CONCLUSIONS: These studies suggest that the expression of a superantigen by S. aureus alone does not play an important role in the increased skin inflammation associated with staphylococcal infection in childhood AD.

Secondary amenorrhoea with high inhibin B level caused by parasitic ovarian leiomyoma.

A 35-year-old patient attended the clinic after 1 year of primary infertility and 9 years secondary amenorrhoea. Her BMI was 21.9 kg/m². Transvaginal scan examination showed a small uterus with 1.7 mm thick endometrium. The left ovary was quiescent and measured 2.9 cm x 61.2 cm x 62.1 cm. 3D images manipulation showed a large (96.9 cm³) solid mass attached to the right ovary. Follicle stimulating hormone (FSH) level was 3.8 IU/l, oestradiol was 57 pmol/l and testosterone was 0.9 nmol/l. She had normal thyroid indices, serum prolactin, 17-hydroxyprogesterone and cortisol levels. Inhibin B and luteinising hormone (LH) blood levels were high at 408 pg/ml and 19.5 IU/l, respectively. The mass was shelled laparoscopically off the right ovary, and proved histologically to be a parasitic leiomyoma. She resumed regular menstruation 1 month after surgery and conceived in her fourth cycle. To the best of our knowledge, this is the first case to be reported relating high inhibin B and luteinising hormone blood levels to an ovarian leiomyoma.

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.

Coexistence of polycystic ovaries and uterine fibroids and their combined effect on the uterine artery blood flow in relation to age and parity.

OBJECTIVE: To examine the coexistence of fibroids and ultrasonically diagnosed polycystic ovaries (PCO) and their combined effects on the uterine artery blood flow in relation to age and parity in women with regular menstruation. STUDY DESIGN: One thousand seventy women, 18-40 years old, with gynecologic or infertility problems, were investigated with transvaginal ultrasound for uterine fibroids and PCO. A subgroup of 468 patients with regular cycles had repeated examinations up to ovulation time. Midcycle mean uterine artery pulsatility index (PI) and Doppler pulse waveform patterns were examined in relation to age, parity, PCO and fibroids. Cross tabulation with chi2 and ANOVA were used for data analysis. A two-tailed p value < 0.05 was taken as significant. RESULTS: One hundred eleven of 343 patients > 35 years old (32.4%) had PCO compared to 479/727 younger women (65.9%) (p < 0.001). Furthermore, fewer patients with PCO (67 of 590, 11.4%) had fibroids as compared to patients with normal ovaries (131 of 480, 27.3%) (p < 0.001). This negative correlation was maintained irrespective of age, parity or ethnic origin. PCO were associated with higher uterine artery PI and more unfavourable Doppler pulse waveform patterns in women < 35 years old and nulliparous women. This effect was not maintained in parous women and those > or = 35 years old. Fibroids did not alter the effect of PCO but increased the uterine artery blood flow in patients with normal-looking ovaries. CONCLUSION: The effect of PCO on the uterine artery blood flow is modulated by age and parity but not by fibroids, which are less common in women with PCO.

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.

Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens.

In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins. Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 15-41% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested. These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fc epsilon-receptor bearing cells armed with the relevant IgE antitoxin.

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.

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.

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.

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.

Staphylococcal toxins and protein A differentially induce cytotoxicity and release of tumor necrosis factor-alpha from human keratinocytes.

It has been proposed that toxins and other bacterial protein products of Staphylococcus aureus can act as triggers or persistence factors in several inflammatory skin diseases. In this study, we examined the S. aureus isolates from the skin of patients with atopic dermatitis and psoriasis. We found that the bacterial isolates from these patients exhibited either characteristic superantigenic toxins or thermolabile toxins believed to be staphylococcal alpha-toxin. All of these staphylococcal strains also secreted extracellular staphylococcal protein A. We found significant differences in the action of these toxins on human keratinocytes and keratinocyte cell lines. The superantigenic toxins toxic shock syndrome toxin-1, staphylococcal enterotoxins A and B, and exfoliative toxin-A, as well as staphylococcal protein A, did not induce significant cytotoxic damage in the keratinocyte cell line HaCaT, whereas the staphylococcal alpha-toxin produced profound cytotoxicity. Keratinocyte cytotoxicity induced by staphylococcal alpha-toxin was time and concentration dependent and demonstrated the morphologic and functional characteristics of necrosis, not apoptosis. Addition of alpha-toxin to keratinocytes simultaneously induced cell lysis and tumor necrosis factor-alpha release into the medium within 30 min; apparently, it was constitutive tumor necrosis factor-alpha. On the other hand, superantigenic toxins and, in particular, protein A showed stimulation of tumor necrosis factor-alpha secretion in keratinocytes and release of this cytokine after 6-12 h of incubation. Thus, staphylococcal protein A, alpha-toxin, and superantigenic toxins found in S. aureus isolates from patients with psoriasis and atopic dermatitis can produce direct pro-inflammatory effects on keratinocytes through the release of tumor necrosis factor-alpha. We propose that these effects may be relevant to the induction and persistence of lesions in these two diseases.