Thoracoscopic Guided Pericostal Sutures as a Solid Fixation for Primary Closure of Congenital Diaphragmatic Hernias.

Purpose: To describe a minimally invasive technique with primary closure and strong suture connection that is feasible in cases of larger, most common type B defects of congenital diaphragmatic hernia (CDH). Background: The thoracoscopic approach (TA) is a favorable technique for the repair of CDH and is still evolving globally. A common issue is finding the optimal suture technique for secure closure in order to prevent recurrences. Whether a defect can be closed only by sutures or by using a patch depends on the size of CDH, the presence of a muscular rim along the inner thoracic surface and finally on the surgeon's experience. From a geometrical point of view, the challenge is to transform the circular defect into a line, without tension, with a strong compound and preferably without additional material. To address this, we apply a setting of the sutures in a "T-shape" and a way to lead the sutures around the rib bones in order to increase stability. This method allows for the primary closure of CDHs and also applies to larger defects. Cases: We present seven newborns with posterolateral CDH on the left side. The defects were solely repaired by TA and by the suturing technique described in detail.

Febrile seizures: perceptions and knowledge of parents of affected and unaffected children.

Febrile seizures (FS) in children are common, but little is known about parents' perceptions and knowledge of FS. We interviewed parents of children aged 6 months to 6 years affected by FS (FS group, 65 parents) or unaffected (control group, 54 parents). In the FS group, 32% said they knew their child had an FS when the first event occurred, and 89% described fear when the child had a seizure, with a median intensity of 10/10 (Q25/Q75: 9/10). Related to follow-up, 77% in the FS group (will) observe their child more carefully after the first seizure happened, and 63% (will) give antipyretics earlier at a median temperature of 38.2 °C (100.8 °F). In the FS group, 62% were unaware of FS before the first event (54% of control group did not know about FS thus far, n.s.). In the FS group, 20% would put a solid object in the mouth of a child having a seizure (control group, 39%, p = 0.030), and 92% would administer an available anti-seizure rescue medication (control group, 78%, p = 0.019). In the FS group, 71% feared that children with FS might suffocate (control group, 70%, n.s.). CONCLUSION: Information about FS and their management should be more available to improve parents' coping and patient safety. WHAT IS KNOWN: • Febrile seizures in children are common. • The prognosis of children suffering from febrile seizures is usually rather good. WHAT IS NEW: • Over half of parents had not informed themselves about febrile seizures so far; and only 32% of parents realized their child had a febrile seizure when it occurred. • Most parents described own fear with a median intensity of 10/10; and 63% (will) give antipyretics earlier at a median temperature of 38.2 °C (100.8 °F).

Aluminium-Catalyzed C(sp)-H Borylation of Alkynes.

Historically used in stoichiometric hydroalumination chemistry, recent advances have transformed aluminium hydrides into versatile catalysts for the hydroboration of unsaturated multiple bonds. This catalytic ability is founded on the defining reactivity of aluminium hydrides with alkynes and alkenes: 1,2-hydroalumination of the unsaturated π-system. This manuscript reports the aluminium hydride catalyzed dehydroborylation of terminal alkynes. A tethered intramolecular amine ligand controls reactivity at the aluminium hydride centre, switching off hydroalumination and instead enabling selective reactions at the alkyne C-H σ-bond. Chemoselective C-H borylation was observed across a series of aryl- and alkyl-substituted alkynes (21 examples). On the basis of kinetic and density functional theory studies, a mechanism in which C-H borylation proceeds by σ-bond metathesis between pinacolborane (HBpin) and alkynyl aluminium intermediates is proposed.

Hematological malignancies in East Africa-Which cancers to expect and how to provide services.

BACKGROUND: Sub-Saharan Africa (SSA) has an increasing non-communicable disease burden. Tanzania has an incidence of more than 35,000 cancer cases per year with an 80% mortality rate. Hematological malignancies account for 10% of these cases. The numbers will double within the next 10 years due to demographic changes, better diagnostic capabilities and life style changes. Kilimanjaro Christian Medical Centre established a Cancer Care Centre (CCC) in December 2016 for a catchment area of 15 million people in Northern Tanzania. This article aims to display the hematological diagnosis and characteristics of the patients as well as to describe the advancements of hematologic services in a low resource setting. METHODS: A cross-sectional analysis of all hematological malignancies at CCC from December 2016 to May 2019 was performed and a narrative report provides information about diagnostic means, treatment and the use of synergies. RESULTS: A total of 209 cases have been documented, the most common malignancies were NHL and MM with 44% and 20%. 36% of NHL cases, 16% of MM cases and 63% of CML cases were seen in patients under the age of 45. When subcategorized, CLL/SLL cases had a median age was 56.5, 51 years for those with other entities of NHL. Sexes were almost equally balanced in all NHL groups while clear male predominance was found in HL and CML. DISCUSSION: Malignancies occur at a younger age and higher stages than in Western countries. It can be assumed that infections play a key role herein. Closing the gap of hematologic services in SSA can be achieved by adapting and reshaping existing infrastructure and partnering with international organizations.

Enantioselective reduction of N-alkyl ketimines with frustrated Lewis pair catalysis using chiral borenium ions.

Enantioselective reduction of ketimines was demonstrated using chiral N-heterocyclic carbene (NHC)-stabilised borenium ions in frustrated Lewis pair catalysis. High levels of enantioselectivity were achieved for substrates featuring secondary N-alkyl substituents. Comparative reactivity and mechanistic studies identify key determinants required to achieve useful enantioselectivity and represent a step forward in the further development of enantioselective FLP methodologies.

Robotic fenestration of massive liver cysts using EndoWrist technology.

BACKGROUND: We present the short-term outcomes of robotic fenestration of symptomatic liver cysts using the EndoWrist One Vessel Sealer. METHODS: Data from patients who underwent robotic deroofing were collected and analysed retrospectively. RESULTS: A total of 17 patients were treated. Mean cyst size was 14 cm (median 15 cm, range 6.3-24). Seven cysts were in posterosuperior or central segments. There were no mortalities or conversions. Blood loss was minimal in all but one case of 200 ml. Mean operating time was 174 minutes (median 170 min, range 97-335). Mean hospital stay was 2.5 days (median 2 days, range 1-10). One patient developed a bile leak requiring ERCP. There are no recurrences with a median follow-up of 19 months. CONCLUSION: Robotic fenestration can be safely performed and offers distinct advantages over the laparoscopic approach in the treatment of posterosuperior and perihilar cysts at the expense of longer operating times and increased cost.

Stereoretentive Etherification of an α-Aryl-ß-amino Alcohol Using a Selective Aziridinium Ring Opening for the Synthesis of AZD7594.

A selective aziridinium ring-opening was used to etherify an α-aryl-ß-amino alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester impurity. The protecting group strategy was directed by a stability study of the activated α-aryl-ß-amino alcohol in this system. Process analytical techniques were used to establish reaction understanding, and mixing on large scale was modeled in silico. The process provided a selective and efficient method of preparing the nonsteroidal, inhaled selective glucocorticoid receptor modulator AZD7594.

Mechanistic Insight into Palladium-Catalyzed Cycloisomerization: A Combined Experimental and Theoretical Study.

The cycloisomerization of enynes catalyzed by Pd(OAc)2 and bis-benzylidene ethylenediamine (bbeda) is a landmark methodology in transition-metal-catalyzed cycloisomerization. However, the mechanistic pathway by which this reaction proceeds has remained unclear for several decades. Here we describe mechanistic investigations into this reaction using enynamides, which deliver azacycles with high regio- and stereocontrol. Extensive 1H NMR spectroscopic studies and isotope effects support a palladium(II) hydride-mediated pathway and reveal crucial roles of bbeda, water, and the precise nature of the Pd(OAc)2 pre-catalyst. Computational studies support these mechanistic findings and lead to a clear picture of the origins of the high stereocontrol that can be achieved in this transformation, as well as suggesting a novel mechanism by which hydrometalation proceeds.

Broad scope hydrofunctionalization of styrene derivatives using iron-catalyzed hydromagnesiation.

The highly regioselective iron-catalyzed formal hydrofunctionalization of styrene derivatives with a diverse range of electrophiles has been developed using a single, operationally simple hydromagnesiation procedure and only commercially available, bench-stable reagents. Using just 0.5 mol % FeCl2·4H2O and N,N,N',N'-tetramethylethylenediamine, hydromagnesiation and electrophilic trapping have been used to form new carbon-carbon bonds (13 examples) and carbon-heteroatom bonds (5 examples) including the products of formal cross-coupling reactions, hydroboration, hydroamination, hydrosilylation, and hydrofluorination.

Dehydromethylation of alkali metal salts of the utility amide 2,2,6,6-tetramethylpiperidide (TMP).

A general thermolysis reaction for the transformation of Group 1 TMP compounds (LiTMP, NaTMP, KTMP) to 1-aza-allylic TTHP derivatives is reported. TMEDA accelerates the reaction and produces the crystalline complexes [(TMEDA)LiTTHP] and [(TMEDA·NaTTHP)2]. Methane elimination during the transformational process was confirmed via TVA coupled to MS.

Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597.

PURPOSE: Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. PATIENTS AND METHODS: Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200 µg versus placebo daily for 48 months. Participation was 6 to 36 months postoperatively and required a negative mediastinal node biopsy, no excessive vitamin intake, normal liver function, negative chest x-ray, and no other evidence of recurrence. RESULTS: The first interim analysis in October 2009, with 46% of the projected end points accumulated, showed a trend in favor of the placebo group with a low likelihood that the trial would become positive; thus, the study was stopped. One thousand seven hundred seventy-two participants were enrolled, with 1,561 patients randomly assigned. Analysis was updated in June 2011 with the maturation of 54% of the planned end points. Two hundred fifty-two SPTs (from 224 patients) developed, of which 98 (from 97 patients) were lung cancer (38.9%). Lung and overall SPT incidence were 1.62 and 3.54 per 100 person-years, respectively, for selenium versus 1.30 and 3.39 per 100 person-years, respectively, for placebo (P = .294). Five-year disease-free survival was 74.4% for selenium recipients versus 79.6% for placebo recipients. Grade 1 to 2 toxicity occurred in 31% of selenium recipients and 26% of placebo recipients, and grade ≥ 3 toxicity occurred in less than 2% of selenium recipients versus 3% of placebo recipients. Compliance was excellent. No increase in diabetes mellitus or skin cancer was detected. CONCLUSION: Selenium was safe but conferred no benefit over placebo in the prevention of SPT in patients with resected NSCLC.

Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium-mediated zincation chemistry.

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N',N'-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78% and 48% following D2O quenching of zincated benzamide intermediates). An 88% yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP)tBu2] and the post-metallation complex [(TMEDA)Li(cis-DMP){2-[1-C(=O)N(iPr)2]C6H4}Zn(tBu)], shed valuable light on the structures and mechanisms involved in these alkali-metal-mediated zincation reactions. Aspects of these reactions are also modelled by DFT calculations.

Improved care and growth outcomes by using hybrid humidified incubators in very preterm infants.

OBJECTIVE: To identify changes in temperature, fluid and electrolyte management, growth, and short-term outcome in extremely low birth weight (ELBW) infants nursed in humidified hybrid incubators (HI group) compared with a cohort of patients cared for in nonhumidified conventional incubators (CI group). METHODS: Body temperature (BT), fluid and electrolyte balance, and growth velocity (GV) were collected retrospectively on 182 ELBW infants. The CI group included ELBW infants cared for with radiant warmers followed by an incubator without humidity. The HI group included ELBW infants cared for in the radiant warmer mode in a Giraffe OmniBed, followed by the incubator mode using high humidity. RESULTS: The CI group included more multiple births (50.6%) than the HI group (35.8%; P < .05), but there was no difference in demographic characteristics. BT was similar during the first week. The HI group had less fluid intake, urine output, and insensible water loss, less maximum weight loss, and a lower incidence of hypernatremia during the first week than did the CI group (P < .05). The HI group also had a lower frequency of electrolyte sampling and packed red cell transfusion (P < .05), a higher incidence of hyponatremia on postnatal day 1 than the CI group (P < .05), and a higher GV than the CI group (15.2 +/- 5.0 vs 13.5 +/- 4.8 g/kg per day), especially among those with a birth weight of

Total synthesis of complex cyclotryptamine alkaloids: stereocontrolled construction of quaternary carbon stereocenters.

Our ability to access the more complex members of the cyclotryptamine family of alkaloids, and to exploit their disparate biological activities, is limited by the synthetic challenge posed by their oligomeric, polyindoline structures. A recurring structural theme within these molecules is the presence of multiple quaternary stereocenters in close proximity to one another. Over the last decade, we have developed a set of transformations that allow rapid access to polyindolines, a number of which exploit the ability of catalytic levels of palladium to orchestrate carbon-carbon bond formation with impressive levels of regio- and stereocontrol. This review tells the story behind the development of this toolbox of synthetic methods, and their validation through the total synthesis of a number of structurally complex cyclotryptamine alkaloids. It also highlights an aspect of asymmetric catalysis that has received little attention, the ability of catalytic asymmetric reactions to selectively elaborate complex, polyfunctional molecules.

Phorboxazole B synthetic studies: construction of C(1-32) and C(33-46) subtargets.

The convergent syntheses of the C(1-32) and C(33-46) domains of phorboxazole B are described. An iterative cyclocondensation strategy exploited the Jacobsen hetero-Diels-Alder (HDA) reaction as a platform for the synthesis of both the C(5-9) and C(11-15) tetrahydropyran rings. The use of 2-silyloxydiene coupling partners bearing an increasing resemblance to the phorboxazole skeleton was found to lead to a reduction in diastereoselectivity, however, in the case of the C(11-15) ring. The coupling of aldehyde and 2-silyloxydiene by this route provided a C(1-32) fragment which was elaborated to the macrolide core of phorboxazole B. The synthesis of the C(33-46) domain involved a Nozaki-Kishi coupling of aldehyde 31 and vinyl iodide 39. The syntheses of 31 and 39 were highly diastereoselective: an Evans [Cu(Ph-pybox)](SbF6)2-catalysed Mukaiyama aldol reaction formed the cornerstone of the synthesis of 31 whilst a Nagao-Fujita acetate aldol reaction provided a convenient means of installing the sole stereogenic centre of 39.

In vivo whole body and appendicular bone mineral density in rats: a dual energy X-ray absorptiometry study.

Bone mineral density (BMD) of the whole body and hind limb of young adult rats, with and without a sham-operated stifle joint was studied, using dual energy x-ray absorptiometry (DEXA) at three time points. Data from the whole body scan were used for analyses of BMD, bone mineral content (BMC), fat, lean, body weight (BW), percentage of BMC (%BMC), percentage of fat (%fat), and percentage of lean (%lean), none of which were significantly different between the groups at any time point. Significant (P < 0.05) differences in BMD, BMC, %BMC, BW, fat, %fat, and %lean were apparent at the second and third scans, compared with the initial scan, within both groups. Changes in whole body BMD, BMC, and %BMC as well as BW were highly correlated with time in both groups. In the hind limb scans, regions of interest (ROIs) were created to obtain values of BMD and BMC from the whole femur, whole tibia including the fibula, distal portion of the femur, and proximal portion of the tibia. Significant differences were not found between the groups for any ROIs. However, significant BMD and BMC increases were evident in all ROIs at the second and third scans, compared with the initial scan. Similar to those in the whole body scan, BMD and BMC obtained from ROIs were highly correlated with time. The positioning technique for the whole body and appendicular scans was analyzed by calculating percentage of the coefficient of variation (%CV) at the beginning of the study. The %CV was low and acceptable in ROIs for the hind limb and for all parameters of the whole body scan, except fat. The results suggest that in vivo DEXA scanning of the rat whole body and appendicular skeleton is highly reproducible and useful to study the whole skeleton, as well as a region of a long bone of the rat. Values for the sham-operated rats were not significantly different from those for the untreated controls, which suggests that soft tissue damage around the stifle joint did not alter BMD in the subchondral bone of the distal portion of the femur and proximal portion of the tibia.

Posttransplantation lymphoproliferative disorder: manifestations in pediatric thoracic organ recipients.

PURPOSE: To describe and correlate the clinical and imaging features of posttransplantation lymphoproliferative disorder (PTLD) in young thoracic organ transplant recipients. MATERIALS AND METHODS: The authors retrospectively reviewed the medical and imaging records of 31 PTLD episodes in 27 patients with PTLD out of 183 young patients who survived for at least 1 month after thoracic organ transplantation: 18 (14%) heart transplant recipients and nine (16%) lung or heart-lung transplant recipients. Four patients had two separate PTLD episodes. The distribution, timing, and imaging features of the disease were analyzed. RESULTS: Seventeen (55%) of 31 episodes involved intrathoracic PTLD manifesting as multiple pulmonary nodules (n = 10), a solitary nodule (n = 3), alveolar consolidation (n = 3), and/or mediastinal adenopathy (n = 8). Extrathoracic PTLD occurred in 21 (68%) of 31 episodes and involved the abdomen (n = 15), head and neck (n = 11), and/or central nervous system (n = 3). The imaging findings of these episodes included bowel wall thickening, lymphadenopathy, and focal masses. Intrathoracic PTLD occurred more commonly in lung transplant recipients (89%) than in heart transplant recipients (44%); no cases of lymphoma involved the thorax. The frequency of extrathoracic manifestations was higher in heart transplant recipients (83%) than in lung transplant recipients (33%). In lung transplant recipients, the prevalence of early-onset PTLD was significantly greater than that in heart transplant recipients (P <.05). Intrathoracic PTLD tended to manifest early. CONCLUSION: PTLD in young thoracic transplant recipients involves the lungs and extrathoracic organs, tends to have an early onset, and manifests predominantly in the thorax in lung transplant and heart-lung transplant recipients, as opposed to heart transplant recipients.