Left ventricular volume reduction surgery in the middle East

Heart transplantation is not yet socially acceptable in the Middle East, and left ventricular assist facilities are not generally available in this region. Therefore, left ventricular volume reduction surgery was attempted in 41 patients with end-stage heart failure (33 males; median age, 36.3 years) in 4 Middle Eastern tertiary referral centers between February 1996 and January 2001. Heart failure was due to idiopathic cardiomyopathy in 21 patients, ischemia in 11, rheumatic valvular disease in 8, and viral myocarditis in 1. Associated procedures were aortic valve replacement in 5 patients, mitral valve repair in 25, mitral valve replacement in 7, tricuspid valve repair in 6, and coronary bypass grafting in 8. Hospital mortality was 31.7%. Five patients were lost to follow-up. The survival rate of hospital survivors at 18 months was 65.2%. Three of the surviving patients did not benefit from the operation. Although our results were somewhat disappointing, this operation remains an option for surgeons working in developing areas of the world. It is hoped that better patient selection and new techniques of left ventricular volume reduction that avoid resection of viable muscle will further improve the outcome of this operation.     

Immunoglobulin D lambda multiple myeloma and amyloidosis with predominant soft tissue involvement.

Multiple myeloma (MM) is associated with amyloidosis in approximately 15% of the patients. The most frequent presenting signs of such an association are nephrotic syndrome, cardiomyopathy and peripheral neuropathy. Amyloid arthropathy is not a frequent feature. We report a patient with immunoglobulin D (IgD) lambda type MM with presenting symptoms related to mucocutaneous amyloidosis and also amyloid arthropathy. He had no clinical and laboratory involvement due to nephrotic syndrome or cardiomyopathy. IgD myeloma is a rare form of MM and therefore much of the information about the disease is derived from case reports describing patients with associated symptoms. Our case also shows an unusual organ distribution of amyloid.     

Analyzing HLA-G polymorphisms in children from women with scleroderma

Embryos during pregnancy and organs during transplantation, express high levels of soluble HLA-G (sHLA-G) molecules for successful implantation and protection against maternal immune cells or recipient’s cells. We and others have shown that women with scleroderma (SSc) carry cells/DNA arising from pregnancy, so-called fetal microchimerism (Mc) more often and in higher quantities than healthy women decades after delivery.     

New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells

Transmembrane channel-like protein isoform 1 (TMC1) is a major component of the mechano-electrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness. We report a new dominant human deafness mutation, TMC1 p.T422K, and have characterized the homologous mouse mutant, Tmc1 p.T416K, which caused deafness and outer hair cell (OHC) loss by the fourth postnatal week. MET channels showed decreased Ca²⁺ permeability and resting open probability, but no change in single-channel conductance or expression. Three adjacent deafness mutations are TMC1 p.L416R, p.G417R, and p.M418K, the last homologous to the mouse Beethoven that exhibits similar channel effects. All substitute a positive for a neutral residue, which could produce charge screening in the channel pore or influence binding of an accessory subunit. Channel properties were compared in mice of both sexes between dominant (Tmc1 p.T416K, Tmc1 p.D569N) and recessive (Tmc1 p.W554L, Tmc1 p.D528N) mutations of residues near the putative pore of the channel. Tmc1 p.W554L and p.D569N exhibit reduced maximum current with no effect on single-channel conductance, implying a smaller number of channels transported to the stereociliary tips; this may stem from impaired TMC1 binding to LHFPL5. Tmc1 p.D528N, located in the pore''s narrowest region, uniquely caused large reductions in MET channel conductance and block by dihydrostreptomycin (DHS). For Tmc1 p.T416K and Tmc1 p.D528N, transduction loss occurred between P15 and P20. We propose two mechanisms linking channel mutations and deafness: decreased Ca²⁺ permeability, common to all mutants, and decreased resting open probability in low Ca²⁺, confined to dominant mutations.SIGNIFICANCE STATEMENT Transmembrane channel-like protein isoform 1 (TMC1) is thought to be a major component of the mechanotransducer channel in auditory hair cells, but the protein organization and channel structure are still uncertain. We made four mouse lines harboring Tmc1 point mutations that alter channel properties, causing hair cell degeneration and deafness. These include a mouse homolog of a new human deafness mutation pT416K that decreased channel Ca²⁺ permeability by introducing a positively-charged amino acid in the putative pore. All mutations are consistent with the channel structure predicted from modeling, but only one, p.D528N near the external face of the pore, substantially reduced channel conductance and Ca²⁺ permeability and virtually abolished block by dihydrostreptomycin (DHS), strongly endorsing its siting within the pore.     

Determining host factors contributing to disease severity in a family cluster of 29 hospitalized SARS‐CoV‐2 patients: Could genetic factors be relevant in the clinical course of COVID‐19?

In this study, we report a large family cluster consisting of 29 genetically related patients hospitalized with coronavirus disease‐2019 (COVID‐19). We sought to determine the clinical characteristics relevant to the clinical course of COVID‐19 by comparing the family cluster to unrelated patients with SARS‐CoV‐2 infection so that the presence of potential determinants of disease severity, other than traditional risk factors previously reported, could be investigated. Twenty‐nine patient files were investigated in group 1 and group 2 was created with 52 consecutive patients with COVID‐19 having age and gender compatibility. The virus was detected for diagnosis. The clinical, laboratory and imaging features of all patients were retrospectively screened. Disease course was assessed using records regarding outcome from patient files retrospectively. Groups were compared with respect to baseline characteristics, disease severity on presentation, and disease course. There was no difference between the two groups in terms of comorbidity and smoking history. In terms of inhospital treatment, use differed not significantly between two groups. We found that all 29 patients in the group 1 had severe pneumonia, 18 patients had severe pneumonia. Hospitalization rates, length of hospital stay, and transferred to intensive care unit were found to be statistically significantly higher in the group 1. In the present study, COVID‐19 cases in the large family cluster were shown to have more severe disease and worse clinical course compared with consecutive patients with COVID‐19 presenting to the same time. We believe further studies into potential genetic mechanisms of host susceptibility to COVID‐19 should include such family clusters.     

Primary dural lymphoma: A novel concept of heterogeneous disease

Spinal primary dural lymphoma (PDL) is uncommon with a total of 37 previous well‐documented cases reported, including one diagnosed in the authors' institution. More recently we encountered an additional case of spinal PDL that, similarly to our previous case, was grade 1–2 follicular B‐cell PDL. Our two cases were diagnosed over a 3‐year interval in a 72‐year‐old female and a 74‐year‐old male, respectively. An exhaustive literature review on PDL was performed consequently to reveal that: (i) spinal and cerebral sites of involvement by PDL are constantly mutually exclusive; and (ii) unlike cerebral PDL, which is usually of marginal zone B‐cell type, only two of the 38 cases of spinal PDL were diagnosed as such, diffuse large B‐cell lymphoma being the most commonly encountered type in the spine. This divergence infers that, in contrast to the prevailing concept that PDL is a unique disease group, PDL appears to be rather heterogeneous with a difference in predilection of lymphoma type for the anatomical site of dural involvement. Such a site‐specific lymphoma‐type predilection phenomenon, well‐recognized in other organ systems, has not been acknowledged in PDL. This report brings new insights into PDL, and may contribute to a better understanding of nervous system pathophysiology and lymphoma classification.     

Droplet fluid infusion into a dust layer in relation to self-cleaning

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets. Influence of droplet hydrostatic pressure on the fluid infusion into dust layer is also investigated towards exploring the dust removal mechanisms. Environmental dust characteristics are evaluated and their interface with the droplet fluid is assessed. Sets of experiments are carried out to examine: (i) droplet fluid infusion into the dust layer, (ii) droplet fluid cloaking of dust, and (iii) evaluate the weight gain of the dust particles during cloaking. The findings reveal that droplet fluid (water) spreads onto the dusty surface and infuses on the dust particles. Cloaking velocity decays sharply with time and the weight gain of the dust particles is about 17% of the original dust weight after cloaking. The dust particles have a large area of nano-size open-pores-sites on the surface; however, capillary diffusion through these sites is limited with shallow depths and the weight gain of a dust particle via capillary diffusion is about 1% of the particle weight. The maximum infusion depth of the droplet fluid in the dust layer is about 74 μm, which is slightly less than the dust layer thickness on the surface. The rolling droplet picks up all the dust from the 150 μm thick dust layer on the surface.

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets.